Miracle-dz/UniFAR-FTUs huggingface dataset:
The Forkhead Transcription Factor, FOXP3, Is Required for Normal Pituitary Gonadotropin Expression in Mice1

ABSTRACT The hypothalamic-pituitary-gonadal axis is central to normal reproductive function. This pathway begins with the release of gonadotropin-releasing hormone in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound by receptors on gonadotroph cells in the anterior pituitary gland and stimulates the synthesis and secretion of luteinizing hormone and, to some extent, follicle-stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads begin gametogenesis and the synthesis of sex hormones. In humans, mutations of the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are infertile. To understand why FOXP3 is required for reproductive function, we are investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3sf/Y). Although the gonadotroph cells appear to be intact in Foxp3sf/Y mice, luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb) expression are significantly decreased, demonstrating that these mice exhibit a hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing hormone is not significantly decreased in Foxp3sf/Y males. Treatment of Foxp3sf/Y males with a gonadotropin-releasing hormone receptor agonist does not rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3 expression in the pituitary or hypothalamus, suggesting that the infertility seen in Foxp3sf/Y males is a secondary effect, possibly due to loss of FOXP3 in immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and prolactin (Prl) are significantly reduced in Foxp3sf/Y males, whereas the precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to destruction of the thyroid gland by autoimmune cells. We find that Foxp3sf/Y mice have elevated expression of thyroid-stimulating hormone beta (Tshb), suggesting that they may suffer from thyroiditis as well. Expression of the pituitary transcription factors, Pitx1, Pitx2, Lhx3, and Egr1, is normal; however, expression of Foxl2 and Gata2 is elevated. These data are the first to demonstrate a defect at the pituitary level in the absence of FOXP3, which contributes to the infertility observed in mice with Foxp3 loss of function mutations.
The application of intelligent hybrid techniques for the mass appraisal of residential properties

Hybrid systems as the next generation of intelligent applications within the field of mass appraisal and valuation are investigated. Motivated by the obvious limitations of paradigms that are being used in isolation or as stand‐alone techniques such as multiple regression analysis, artificial neural networks and expert systems. Clearly, there are distinct advantages in integrating two or more information processing systems that would address some of the discrete problems of individual techniques. Examines first, the strategic development of mass appraisal approaches which have traditionally been based on “stand‐alone” techniques; second, the potential application of an intelligent hybrid system. Highlights possible solutions by investigating various hybrid systems that may be developed incorporating a nearest neighbour algorithm (k‐NN). The enhancements are aimed at two major deficiencies in traditional distance metrics; user dependence for attribute weights and biases in the distance metric towards matching categorical variables in the retrieval of neighbours. Solutions include statistical techniques: mean, coefficient of variation and significant mean. Data mining paradigms based on a loosely coupled neural network or alternatively a tight coupling with genetic algorithms are used to discover attribute weights. The hybrid architectures developed are applied to a property data set and their performance measured based on their predictive value as well as perspicuity. Concludes by considering the application and the relevance of these techniques within the field of computer assisted mass appraisal.
Inducible bronchus-associated lymphoid tissue (iBALT) synergizes with local lymph nodes during antiviral CD4+ T cell responses.

BACKGROUND Exposure of the lungs to an antigen or pathogen elicits the formation of lymphoid satellite islands termed inducible bronchus-associated lymphoid tissue (iBALT). However, little is known about how the presence of iBALT, induced by a stimulus unrelated to the subsequent challenge agent, influences systemic immunity in distal locations, whether it be independently, antagonistically, or synergistically. Here, we determined the kinetics of the influenza-specific responses in the iBALT, tracheobronchial lymph node (TBLN), and spleen of mice with and without pre-formed iBALT. METHODS AND RESULTS Mice with VLP-induced iBALT or no pre-formed iBALT were challenged with influenza. We found that, as we have previously described, those mice whose lungs contained pre-formed iBALT were protected from morbidity, and furthermore, that these mice had increased dendritic cell, and alveolar macrophage accumulation in both the iBALT and TBLNs. This translated to similarly accelerated kinetics and intensified influenza-specific CD4(+), but not CD8(+) T cell responses in the iBALT, TBLN, and spleen. This expansion was then followed by a more rapid T cell contraction in all lymphoid tissues in the mice with pre-formed iBALT. CONCLUSIONS Thus, iBALT itself may not be responsible for the accelerated primary immune response we observe in mice with pre-formed iBALT, but may contribute to an overall accelerated local and systemic primary CD4(+), but not CD8(+) T cell response. Furthermore, less damaging immune responses observed in mice with pre-formed iBALT may be due to a quicker contraction of CD4(+) T cell responses in both local and systemic secondary lymphoid tissue.
A ZnO-rGO composite thin film discrete memristor

Ultrathin 2D materials such as TiO2, WOx, NiO, ZnO, VO2 and graphene, offer scope for low power, highly dense and ultra-fast electronic devices. Due to their extraordinary physical and electrical/electronic property. In this work, a novel forming free memristor has been realized based on hybrid film of ZnO-rGO. The structure of the device is Metal-Insulator-Metal structure, where the Zinc Oxide- Reduced Graphene Oxide (ZnO-rGO) thin film is sandwiched between Silver (Ag) and Fluorine-doped tin oxide (FTO) coated glass. Free oxygen vacancies were created within the composite film by using high temperature annealing at 500 degrees Celsius. We demonstrate bipolar resistive switching behavior of the new device. Also we show that the variation of the conductance of the device is related to delay time of the applied input voltage sweep.
A Century of Research on Agricultural Markets

This article provides a perspective on major innovations in research on agricultural markets over the past century. We review research on market structure and performance, vertical coordination arrangements, and institutions for producer collective action. Contributions to empirical modeling of agricultural price determination and marketing margins are also evaluated, as are innovations in research on spatial market relationships and the role of storage. Finally, we discuss contributions to understanding market information systems and the functioning of market-based mechanisms for agricultural risk management, including futures, options, and insurance. Although progress over the century has been remarkable, we conclude by highlighting possible directions for future research. Copyright 2010, Oxford University Press.
Genetic Composition of Mycobacterium bovis BCG Substrain Sofia

Mycobacterium bovis BCG remains the most widely used vaccine in the world, with a range of substrains that are named after their locations of production. More than 40 million doses of the BCG substrain Sofia are distributed annually through the United Nations Children’s Fund (UNICEF) and the Pan American Health Organization (PAHO) to approximately 120 different countries. However, in spite of its widespread use BCG Sofia has never been investigated at the genetic level, raising questions as to its genetic stability and exact provenance. The Bulgarian BCG Laboratory was established in 1949 when Dr. Srebra Rodopska obtained the BCG strain from the Institute Pasteur. However, due to suppurative cervical lymphadenitis in about 1% of orally vaccinated newborns, a few years later it was replaced with the Russian BCG strain. During 1972 lot 222 was approved as a master seed lot, originating the BCG substrain Sofia SL222. A working seed lot was produced from the master in 1993 from which all commercial lots are currently produced. To investigate the genetic properties of BCG Sofia, including its position on the BCG genealogical tree developed by Behr and colleagues (1), we performed genotyping assays on the master and working seed lots and on commercial batches no. 906 and 909 of BCG Sofia. We initially concentrated on genomic loci that are prone to variation. Spoligotyping exploits a polymorphic direct repeat (DR) locus that is composed of multiple 36-bp DR copies interspersed by unique spacers, with strains varying in the presence or absence of spacers (4). No difference among any of the BCG Sofia lots tested was found, with all strains showing patterns identical to those of other BCGs. Variable number of tandem repeat (VNTR) typing targeted six alleles (A through F [2]) that vary in the length and number of repeats at each target; i.e., 7-5-5-4-3-3 would have 7 copies of allele A, 5 of B, etc. (2). The VNTR profile of BCG Sofia was determined to be 5-5-5-2-3-3.1, which is identical to the profiles of all other BCG strains tested. A whole-genome analysis of BCG Sofia was undertaken by using M. tuberculosis microarrays (5). This disclosed a range of deletions and a duplication that places BCG Sofia in the same lineage as BCG Russia, in accordance with the BCG genealogy. However, a novel 1.6-kb deletion that affects the Rv3697c and Rv3698 homologues was revealed. To determine whether this deletion had occurred during in vitro propagation of BCG Sofia, we screened for this region in other BCG strains. The region was also deleted in BCG Russia but not in any other strain. Hence, this deletion occurred prior to the in vitro cultivation of BCG Sofia. Public concern over the safety of various vaccines demands that they should be described in exquisite detail (3). Our analyses show that BCG Sofia and BCG Russia are indistinguishable, although this does not preclude the existence of single nucleotide changes between the strains. We have therefore confirmed the genetic identity and provenance of a BCG vaccine that is given to over 40 million individuals a year.
N,N'-dimethylpyrazinediium bis(tetrafluoroborate) and N,N'-diethylpyrazinediium bis(tetrafluoroborate): new examples of anion-pi triads.

Crystallization of N,N'-dimethylpyrazinediium bis(tetrafluoroborate), C(6)H(10)N(2)(2+). 2BF(4)(-), (I), and N,N'-diethylpyrazinediium bis(tetrafluoroborate), C(8)H(14)N(2)(2+). 2BF(4)(-), (II), from dried acetonitrile under argon protection has permitted their single-crystal studies. In both crystal structures, the pyrazinediium dications are located about an inversion center (located at the ring center) and each pyrazinediium aromatic ring is pi-bonded to two centrosymmetrically related BF(4)(-) anions. Strong anion-pi interactions, as well as weak C-H.F hydrogen bonds, between BF(4)(-) and pyrazinediium ions are present in both salts.
Novel 18F-Labeled Arylquinoline Derivatives for Noninvasive Imaging of Tau Pathology in Alzheimer Disease

Neurofibrillary tangles in Alzheimer disease (AD) brains are composed of the microtubule-associated protein tau. Noninvasive monitoring of tau protein aggregates in the living brain will provide useful information regarding tau pathophysiology in AD. However, no PET probes are currently available for selective detection of tau pathology in AD. We have previously reported 18F-labeled THK-523 (18F-6-(2-fluoroethoxy)-2-(4-aminophenyl)quinoline) as a tau imaging radiotracer candidate for PET. After compound optimization, we developed novel 18F-labeled arylquinoline derivatives, 18F-THK-5105 and 18F-THK-5117, for use as tau imaging PET tracers. Methods: 18F-labeled compounds were prepared from the corresponding tosylated precursors. The binding affinity of compounds to synthetic tau aggregates and tau-rich AD brain homogenates was determined by saturation and competition binding assays. The binding selectivity of compounds to tau pathology was evaluated by autoradiography of AD brain sections. The pharmacokinetics of compounds were assessed in biodistribution studies in normal mice. A 14-d toxicity study with intravenous administration of compounds was performed using rats and mice. Results: In vitro binding assays demonstrated higher binding affinity of THK-5105 and THK-5117 than THK-523 to tau protein aggregates and tau-rich AD brain homogenates. Autoradiographic analyses of AD brain sections showed that these radiotracers preferentially bound to neurofibrillary tangles and neuropil threads, which colocalized with Gallyas-positive and immunoreactive tau protein deposits. The distribution of this radiotracer binding in AD brain sections was completely different from that of 11C-Pittsburgh compound B, showing preferential binding to amyloid plaques. Furthermore, these derivatives demonstrated abundant initial brain uptake and faster clearance in normal mice than 18F-THK-523 and other reported 18F-labeled radiotracers. THK-5105 and THK-5117 showed no toxic effects related to the administration of these compounds in mice and rats and no significant binding for various neuroreceptors, ion channels, and transporters at 1-μM concentrations. Conclusion: 18F-labeled THK-5105 and THK-5117 are promising candidates as PET tau imaging radiotracers.
An investigation into direct scoring methods without SVM training in speaker verification

In the paper, we ﬁrst propose a new method to handle the problem of scoring a test utterance against a speaker model in the JFA Speaker Veriﬁcation System, called Symmetric Scoring. The SS method is derived from the GMM log-likelihood-ratio approximation and is both symmetrical and efﬁcient. Then we show that SS method and the JFA-SVM system using GMM super-vector space as input have nearly the same form in scoring phase. We also show that the performance of SS method is better than the JFA-SVM system, which indicates that applying the KL kernel function directly to obtain a score in GMM super-vector space is as effective as the JFA-SVM trained using the same kernel. As an inspiration of this direct scoring method in which kernel function is only used to calculate score without SVM training procedure, we try to extend the relationship to speaker factor space and evaluate some results based on different kernels.
Ordinal Ranking with Intensity of Preference

In conventional ordinal ranking models the voter/ranker supplies an ordered set of preferences on a collection of objects without specifying any form of intensity of preference. For example, an executive committee of ten members is required to assign five candidates to five positions. The nature of the positions is such that position one requires the highest qualified candidate (relative to a given attribute), position two the second qualified person and so on. Each one of the members in the committee is required, therefore, to supply a ranking of the five candidates and from each individual preference the committee must come up with an aggregate or consensus ranking which dictates the assignments of the candidates to the jobs. In many situations, however, it is desirable to permit the individual to express some measure of intensity of preference. For example, suppose that six committee members agreed that candidate number one is slightly better than candidate number two, but four of them evaluated candidate number two as being much better than candidate number one. The question now is whether this situation is identical to the case where the six members evaluate candidate one as much better than candidate two and four members evaluate candidate two as slightly better than candidate one. The ordinal ranking model will not distinguish between the above two cases while it is clear that when taking account of the intensity of preference, the committee should end up with two different consensus rankings. This paper develops a model for aggregating ordinal rankings in which the voter is allowed to express such intensity of preferences, and a method to derive the consensus ranking is proposed.
Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas

Human WHO grade 1 meningiomas are generally considered benign tumors; despite this, they account for ≈50% of all recurrent meningiomas. Currently, limited data exist about the mutational profiles of grade 1 meningiomas and patient outcome. We investigated the genetic variants present in 32 WHO grade 1 meningiomas using whole exome sequencing, and correlated gene mutational profiles with tumor cytogenetics and patient outcome. Overall, WHO grade 1 meningiomas harbored numerous and heterogeneous genetic variants, which most frequently affected the NF2 (47%) gene and to a less extent the PNMA6A (22%), TIGD1 (16%), SMO (13%), PTEN (13%), CREG2 (9%), EEF1A1 (6%), POLR2A (6%), ARID1B (3%), and FAIM3 (3%) genes. Notably, non-synonymous genetic variants of SMO and POLR2A were restricted to diploid meningiomas, whereas NF2 mutations were only found among tumors that showed -22/22q─ (with or without a complex karyotype). Based on NF2 mutations and tumor cytogenetics, four genetic profiles were defined with an impact on patient recurrence-free survival (RFS). These included (1) two good-prognosis tumor subgroups—diploid meningiomas (n=9) and isolated -22/22q─ associated with NF2 mutation (n=7)—with RFS rates at 10 y of 100%; and (2) two subgroups of poor-prognosis meningiomas—isolated -22/22q─ without NF2 mutation (n=3) and tumors with complex karyotypes (n=11)—with a RFS rate at 10 y of 48% (p=0.003). Our results point out the existence of recurrent but heterogeneous mutational profiles in WHO grade 1 meningiomas which have an impact on patient outcome.
Analysis of variation in demand and performance of urban expressways using dynamic path flow estimation

Understanding the dynamic characteristics of traffic demand is a key issue in designing a more reliable transport network. Identifying variations in link flow is easy, but it is impossible to determine variations in demand directly from observed traffic data. In this study, demand fluctuation was analysed using the dynamic path flow estimation method. Path flows were estimated using 1 year data from the Hanshin Expressway in Japan, and demand variations were analysed using the estimated results. This article also discusses the relationship between demand variations and external conditions such as weather and commercial practises. The results provide a valuable background for more detailed traffic control measures.
KP elements repress P‐induced hybrid dysgenesis in Drosophila melanogaster.

Molecular and genetic analysis has revealed a specific P factor deletion derivative (the KP element) which is able to repress P‐induced hybrid dysgenesis. All naturally occurring strains lacking the P cytotype (M′) that were examined, throughout the world contain up to 30 copies of KP per haploid genome together with complete P factors. The KP element is derived from the P factor by an internal deletion of 1753 bp removing nucleotides 808‐2560 and is transcribed to yield an abundant 0.8‐kb poly(A)+ RNA with the coding capacity for an in‐frame 207 amino acid polypeptide. Genetic crosses show that KP elements preferentially accumulate in the presence of P factors and suppress hybrid dysgenesis. Suppression is transmitted through both sexes and is thus distinct from the maternally transmitted P cytotype mode of suppression. The spread of KP elements is probably due to the continual selection of individuals with the highest numbers of KP elements in which P‐induced hybrid dysgenesis is suppressed.
Authentic Concepts

Increasingly, tourism businesses introduce authentic concepts to address tourists’ search for authentic and natural experiences. This research investigates how such concepts influence tourists’ experiences. A field experiment was carried out at four mountain lodges where two authentic concepts—a local meal concept and a storytelling concept—were offered to some tourists but not others. Results showed a significant moderator effect of each of the two authentic concepts on the relationship between attribute satisfaction and overall satisfaction; when tourists experienced the authentic concepts, the influence of food and service satisfaction on overall satisfaction became stronger. These results indicate that introducing authentic concepts may strengthen the importance weight tourists place on relevant aspects of experience during evaluation.
Mutation in Irf8 Gene (Irf8R294C ) Impairs Type I IFN-Mediated Antiviral Immune Response by Murine pDCs

Plasmacytoid dendritic cells (pDCs) are the key producers of type I interferons (IFNs), thus playing a central role in initiating antiviral immune response. Besides robust type I IFN production, pDCs also act as antigen presenting cells post immunogenic stimulation. Transcription factor Irf8 is indispensable for the development of both pDC and cDC1 subset. However, the mechanism underlying the differential regulation by IRF8 in cDC1- and pDC-specific genomic architecture of developmental pathways still remains to be fully elucidated. Previous studies indicated that the Irf8R294 C mutation specifically abrogates development of cDC1 without affecting that of pDC. In the present study using RNA-seq based approach, we have found that though the point mutation Irf8R294 C did not affect pDC development, it led to defective type I IFN production, thus resulting in inefficient antiviral response. This observation unraveled the distinctive roles of IRF8 in these two subpopulations—regulating the development of cDC1 whereas modulating the functionality of pDCs without affecting development. We have reported here that Irf8R294 C mutation also caused defect in production of ISGs as well as defective upregulation of costimulatory molecules in pDCs in response to NDV infection (or CpG stimulation). Through in vivo studies, we demonstrated that abrogation of type I IFN production was concomitant with reduced upregulation of costimulatory molecules in pDCs and increased NDV burden in IRF8R294C mice in comparison with wild type, indicating inefficient viral clearance. Further, we have also shown that Irf8R294 C mutation abolished the activation of type I IFN promoter by IRF8, justifying the low level of type I IFN production. Taken together, our study signifies that the single point mutation in Irf8, Irf8R294 C severely compromised type I IFN-mediated immune response by murine pDCs, thereby causing impairment in antiviral immunity.
Random Profits and Duality

Dual production specifications derived under certainty are typically randomized for econometric purposes with ad hoc error specifications. This article shows that such approaches can cause integrability conditionsto fail. In particular, if errorsin input demands represent errorsin optimization that affect output, then typical dual approachesdo not yield congruent suppliesand demands. Copyright 2002, Oxford University Press.