Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairments in cognition and neural precursor cell proliferation in mice expressing constitutively active glycogen synthase kinase-3

Brain glycogen synthase kinase-3 (GSK3) is hyperactive in several neurological conditions that involve impairments in both cognition and neurogenesis. This raises the hypotheses that hyperactive GSK3 may directly contribute to impaired cognition, and that this may be related to deficiencies in neural precursor cells (NPC). To study the effects of hyperactive GSK3 in the absence of disease influences, we compared adult hippocampal NPC proliferation and performance in three cognitive tasks in male and female wild-type (WT) mice and GSK3 knockin mice, which express constitutively active GSK3. NPC proliferation was ~40% deficient in both male and female GSK3 knockin mice compared with WT mice. Environmental enrichment (EE) increased NPC proliferation in male, but not female, GSK3 knockin mice and WT mice. Male and female GSK3 knockin mice exhibited impairments in novel object recognition, temporal order memory, and coordinate spatial processing compared with gender-matched WT mice. EE restored impaired novel object recognition and temporal ordering in both sexes of GSK3 knockin mice, indicating that this repair was not dependent on NPC proliferation, which was not increased by EE in female GSK3 knockin mice. Acute 1 h pretreatment with the GSK3 inhibitor TDZD-8 also improved novel object recognition and temporal ordering in male and female GSK3 knockin mice. These findings demonstrate that hyperactive GSK3 is sufficient to impair adult hippocampal NPC proliferation and to impair performance in three cognitive tasks in both male and female mice, but these changes in NPC proliferation do not directly regulate novel object recognition and temporal ordering tasks.
Mutational Dissection of Telomeric DNA Binding Requirements of G4 Resolvase 1 Shows that G4-Structure and Certain 3’-Tail Sequences Are Sufficient for Tight and Complete Binding

Ends of human chromosomes consist of the six nucleotide repeat d[pTTAGGG]n known as telomeric DNA, which protects chromosomes. We have previously shown that the DHX36 gene product, G4 Resolvase 1 (G4R1), binds parallel G-quadruplex (G4) DNA with an unusually tight apparent Kd. Recent work associates G4R1 with the telomerase holoenzyme, which may allow it to access telomeric G4-DNA. Here we show that G4R1 can tightly bind telomeric G4-DNA, and in the context of the telomeric sequence, we determine length, sequence, and structural requirements sufficient for tight G4R1 telomeric binding. Specifically, G4R1 binds telomeric DNA in the K+-induced “3+1” G4-topology with an apparent Kd = 10 ±1.9 pM, a value similar as previously found for binding to unimolecular parallel G4-DNA. G4R1 binds to the Na+-induced “2+2” basket G4-structure formed by the same DNA sequence with an apparent Kd = 71 ± 2.2 pM. While the minimal G4-structure is not sufficient for G4R1 binding, a 5’ G4-structure with a 3’ unstructured tail containing a guanine flanked by adenine(s) is sufficient for maximal binding. Mutations directed to disrupt G4-structure similarly disrupt G4R1 binding; secondary mutations that restore G4-structure also restore G4R1 binding. We present a model showing that a replication fork disrupting a T-loop could create a 5’ quadruplex with an opened 3’tail structure that is recognized by G4R1.
Magmatic Dike Resonances Inferred from Very-Long-Period Seismic Signals

Very-long-period (VLP) signals showing simple decaying harmonic oscillations with periods near 10 seconds and lasting for about 300 seconds were observed in association with an earthquake swarm that occurred beneath Hachijo Island, Japan. Results from the source-mechanism analysis and waveform simulation based on a fluid-filled crack model consistently point to the resonance of a dike filled with a basaltic magma as the source of the VLP signals. Thus, VLP signals can be used to probe the state of the fluid and dynamic processes within a volcanic system.
Image Quality Analysis of High-Density Diffuse Optical Tomography Incorporating a Subject-Specific Head Model

High-density diffuse optical tomography (HD-DOT) methods have shown significant improvement in localization accuracy and image resolution compared to traditional topographic near infrared spectroscopy of the human brain. In this work we provide a comprehensive evaluation of image quality in visual cortex mapping via a simulation study with the use of an anatomical head model derived from MRI data of a human subject. A model of individual head anatomy provides the surface shape and internal structure that allow for the construction of a more realistic physical model for the forward problem, as well as the use of a structural constraint in the inverse problem. The HD-DOT model utilized here incorporates multiple source-detector separations with continuous-wave data with added noise based on experimental results. To evaluate image quality we quantify the localization error and localized volume at half maximum (LVHM) throughout a region of interest within the visual cortex and systematically analyze the use of whole-brain tissue spatial constraint within image reconstruction. Our results demonstrate that an image quality with less than 10 mm in localization error and 1000 m3 in LVHM can be obtained up to 13 mm below the scalp surface with a typical unconstrained reconstruction and up to 18 mm deep when a whole-brain spatial constraint based on the brain tissue is utilized.
Evaluating Phylogenetic Congruence in the Post-Genomic Era

Congruence is a broadly applied notion in evolutionary biology used to justify multigene phylogeny or phylogenomics, as well as in studies of coevolution, lateral gene transfer, and as evidence for common descent. Existing methods for identifying incongruence or heterogeneity using character data were designed for data sets that are both small and expected to be rarely incongruent. At the same time, methods that assess incongruence using comparison of trees test a null hypothesis of uncorrelated tree structures, which may be inappropriate for phylogenomic studies. As such, they are ill-suited for the growing number of available genome sequences, most of which are from prokaryotes and viruses, either for phylogenomic analysis or for studies of the evolutionary forces and events that have shaped these genomes. Specifically, many existing methods scale poorly with large numbers of genes, cannot accommodate high levels of incongruence, and do not adequately model patterns of missing taxa for different markers. We propose the development of novel incongruence assessment methods suitable for the analysis of the molecular evolution of the vast majority of life and support the investigation of homogeneity of evolutionary process in cases where markers do not share identical tree structures.
Calibration of moisture monitors

A method for calibrating an aluminum oxide hygrometer against an optical chilled mirror dew-point hygrometer has been established. A theoretical cross-point line of dew points from both hygrometers and a maximum moisture content of 10 ppM/sub v/ are used to define an area for calibrating the sensor probes of the aluminum oxide hygrometer.
Polar Mapper: a computational tool for integrated visualization of protein interaction networks and mRNA expression data

Polar Mapper is a computational application for exposing the architecture of protein interaction networks. It facilitates the system-level analysis of mRNA expression data in the context of the underlying protein interaction network. Preliminary analysis of a human protein interaction network and comparison of the yeast oxidative stress and heat shock gene expression responses are addressed as case studies.
Graphene reinforced ultra high molecular weight polyethylene with improved tensile strength and creep resistance properties

Reduced graphene oxide or graphene was dispersed in ultra high molecular weight polyethylene (UHMWPE) using two methods to prepare nanocomposite films. In pre-reduction method, graphite oxide (GO) was exfoliated and dis- persed in organic solvents and reduced to graphene before polymer was added, while reduction of graphene oxide was car- ried out after polymer addition for in situ reduction method. Raman spectroscopic study reveals that the second method results in better exfoliation of graphene but it has more amorphous content as evident from selected area electron diffraction (SAED) pattern, wide angle X-ray and differential scanning calorimetry (DSC). The nanocomposite film produced by pre- reduction method possesses higher crystallinity (almost the same as that of the pure film) as compared to the in situ method. It shows better modulus (increased from 864 to 1236 MPa), better strength (increased from 12.6 to 22.2 MPa), network hardening and creep resistance (creep strain reduced to 9% from 50% when 40% of maximum load was applied for 72 h) than the pure film. These findings show that graphene can be used for reinforcement of UHMWPE to improve its tensile and creep resistance properties.
Animal manure phosphorus characterization by sequential chemical fractionation, release kinetics and 31P-NMR analysis

Phosphate release kinetics from manures are of global interest because sustainable plant nutrition with phosphate will be a major concern in the future. Although information on the bioavailability and chemical composition of P present in manure used as fertilizer are important to understand its dynamics in the soil, such studies are still scarce. Therefore, P extraction was evaluated in this study by sequential chemical fractionation, desorption with anion-cation exchange resin and 31P nuclear magnetic resonance (31P-NMR) spectroscopy to assess the P forms in three different dry manure types (i.e. poultry, cattle and swine manure). All three methods showed that the P forms in poultry, cattle and swine dry manures are mostly inorganic and highly bioavailable. The estimated P pools showed that organic and recalcitrant P forms were negligible and highly dependent on the Ca:P ratio in manures. The results obtained here showed that the extraction of P with these three different methods allows a better understanding and complete characterization of the P pools present in the manures.
Pharmacological Targeting of Phosphoinositide Lipid Kinases and Phosphatases in the Immune System: Success, Disappointment, and New Opportunities

The predominant expression of the γ and δ isoforms of PI3K in cells of hematopoietic lineage prompted speculation that inhibitors of these isoforms could offer opportunities for selective targeting of PI3K in the immune system in a range of immune-related pathologies. While there has been some success in developing PI3Kδ inhibitors, progress in developing selective inhibitors of PI3Kγ has been rather disappointing. This has prompted the search for alternative targets with which to modulate PI3K signaling specifically in the immune system. One such target is the SH2 domain-containing inositol-5-phosphatase-1 (SHIP-1) which de-phosphorylates PI(3,4,5)P3 at the D5 position of the inositol ring to create PI(3,4)P2. In this article, we first describe the current state of PI3K isoform-selective inhibitor development. We then focus on the structure of SHIP-1 and its function in the immune system. Finally, we consider the current state of development of small molecule compounds that potently and selectively modulate SHIP activity and which offer novel opportunities to manipulate PI3K mediated signaling in the immune system.
Picard groups in Poisson geometry

We study isomorphism classes of symplectic dual pairs P P-, where P is an integrable Poisson manifold, S is symplectic, and the two maps are complete, surjective Poisson submersions with connected and simply-connected fibres. For fixed P, these Morita self-equivalences of P form a group Pic(P) under a natural ``tensor product'' operation. We discuss this group in several examples and study variants of this construction for rings (the origin of the notion of Picard group), Lie groupoids, and symplectic groupoids.
Influence of nanoclay and coupling agent on the physical and mechanical properties of polypropylene/bagasse nanocomposite

In this work, the effects of nanoclay (1–4 wt %) and coupling agent (2 and 4 wt %) loading on the physical and mechanical properties of nanocomposites are investigated. Composites based on polypropylene (PP), bagasse flour, and nanoclay (montmorillonite type) was made by melt compounding and then compression molding. When 1–3 wt % nanoclay was added, the tensile properties increased significantly, but then decreased slightly as the nanoclay content increased to 4%. The impact strength was 6% lower by the addition of 1 wt % nanoclay, it was decreased further when the nanoclay content increased from 1 to 4%. Finally, the water absorption of PP/bagasse composites was lowered with the increase in nanoclay content. Additionally, the coupling agent, 4 wt % MAPP, improved the mechanical and physical properties of the composites more than the 2 wt % MAPP. From these results, we can conclude that addition of nanoclay enables to achieve better physical and mechanical properties in conventional composites. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
High Vaccination Coverage among Children during Influenza A(H1N1)pdm09 as a Potential Factor of Herd Immunity

The objective of this study was to identify factors related to the expansion of infection and prevention of influenza A(H1N1)pdm09. A retrospective non-randomized cohort study (from June 2009 to May 2010) on influenza A(H1N1)pdm09 was conducted in a sample of residents from Hiroshima Prefecture, Japan. The cumulative incidence of the influenza A(H1N1)pdm09 and the pandemic vaccine effectiveness (VE) were estimated. The response rate was 53.5% (178,669/333,892). Overall, the odds ratio of non-vaccinated group to vaccinated group for cumulative incidence of influenza A(H1N1)pdm09 was 2.18 (95% confidence interval (CI): 2.13–2.23) and the VE was 43.9% (CI: 42.8–44.9). The expansion of infection, indicating the power of transmission from infected person to susceptible person, was high in the 7–15 years age groups in each area. In conclusion, results from this survey suggested that schoolchildren-based vaccination rate participates in determining the level of herd immunity to influenza and children might be the drivers of influenza transmission. For future pandemic preparedness, vaccination of schoolchildren may help to prevent disease transmission during influenza outbreak.
Reactivity and Regulatory Properties of Human Anti-Idiotypic Antibodies Induced by T Cell Vaccination1

Immunization with irradiated autoreactive T cells (T cell vaccination) induces anti-idiotypic T cell responses that preferentially recognize complementarity-determining region 3 sequences, contributing to clonal depletion of autoreactive T cells. However, it remains unknown whether T cell vaccination elicits anti-idiotypic humoral responses and whether the anti-idiotypic Abs play a similar role in the regulatory mechanism induced by T cell vaccination. In this study we examined the occurrence, the reactivity pattern, and the regulatory role of anti-idiotypic Abs elicited by T cell vaccination in patients with multiple sclerosis. We demonstrated for the first time that B cells producing anti-idiotypic Abs could be isolated from vaccinated patients. These EBV-transformed B cell lines were selected for specific reactivity to a 20-mer TCR peptide incorporating a common complementarity-determining region 3 sequence of the immunizing T cell clones. The resulting anti-idiotypic Abs were found to react with the original immunizing T cell clones and exhibit an inhibitory effect on their proliferation. The findings suggest that anti-idiotypic Ab responses can be induced by T cell vaccination in humans and that their regulatory properties are likely to contribute to the suppression of myelin basic protein-reactive T cells in vaccinated patients. The study has important implications in our understanding of the regulatory role of the anti-idiotypic humoral responses induced by T cell vaccination.
Approximate Decomposition: A Method for Bounding and Estimating Probabilistic and Deterministic Queries

In this paper, we introduce a method for approximating the solution to inference and optimization tasks in uncertain and deterministic reasoning. Such tasks are in general intractable for exact algorithms because of the large number of dependency relationships in their structure. Our method effectively maps such a dense problem to a sparser one which is in some sense "closest". Exact methods can be run on the sparser problem to derive bounds on the original answer, which can be quite sharp. On one large CPCS network, for example, we were able to calculate upper and lower bounds on the conditional probability of a variable, given evidence, that were almost identical in the average case.
Overexpression of BAD preferentially augments anoikis

BAD is a BH3‐only protein, and its proapoptotic activity is negatively regulated by serine phosphorylation. Here, we show that overexpression of BAD preferentially augments anchorage loss–induced apoptosis (anoikis). Gene transfer–mediated BAD overexpression alone did not induce apoptosis in attached MDCK cells but strongly augmented apoptosis when cells were cultured in suspension. In contrast, overexpression of another BH3‐only protein, BID, displayed much lower augmentation of anoikis, suggesting a preferential contribution of BAD to anoikis. During suspension culture, unphosphorylated BAD was gradually increased and targeted to the mitochondria. Cotransfection of BAD with constitutively active Akt cDNA strongly inhibited this change. In contrast, the increase of unphosphorylated BAD was not significantly inhibited by several phosphatase inhibitors or cotransfection with a dominant negative calcineurin cDNA, implying that the increase may be mainly due to a decrease of serine kinase activity, such as that of Akt. Similar results were observed in COS‐7 cells, suggesting that BAD overexpression can increase sensitivity of anchorage‐dependent cancer cells to anoikis. Thus, we propose that BAD can serve as a valuable gene therapeutic molecule to inhibit carcinoma progression. © 2003 Wiley‐Liss, Inc.
Quantitative Lower Bounds for the Full Boltzmann Equation, Part I: Periodic Boundary Conditions

ABSTRACT We prove the appearance of an explicit lower bound on the solution to the full Boltzmann equation in the torus for a broad family of collision kernels including in particular long-range interaction models, under the assumption of some uniform bounds on some hydrodynamic quantities. This lower bound is independent of time and space. When the collision kernel satisfies Grad's cutoff assumption, the lower bound is a global Maxwellian and its asymptotic behavior in velocity is optimal, whereas for noncutoff collision kernels the lower bound we obtain decreases exponentially but faster than the Maxwellian. Our results cover solutions constructed in a spatially homogeneous setting, as well as small-time or close-to-equilibrium solutions to the full Boltzmann equation in the torus. The constants are explicit and depend on the a priori bounds on the solution.
Laparoscopic Excision of Coexisting Left Tubal and Right Pseudotubal Pregnancy after Conservative Management of Previous Ectopic Pregnancy with Methotrexate: An Unusual Clinical Entity

Tubal pregnancy concerns 97% of all ectopic pregnancies. Treatment can be either surgical (salpingostomy or salpingectomy) or medical (methotrexate administration). We present a case of a pseudotubal pregnancy after methotrexate treatment of a previous ectopic pregnancy. A37-year-old woman was diagnosed with ectopic pregnancy in the left Fallopian tube. A year ago, she had an ectopic pregnancy in the right tube, which was successfully treated with intramuscular methotrexate. During laparoscopy, two tubal masses were revealed, one in each Fallopian tube, and bilateral salpingectomy was performed. Histological analysis confirmed tubal pregnancy in the left Fallopian tube and presence of endosalpingitis in the right tube with no signs of chorionic villi. The optimal management of such cases has not yet been clarified. However, evaluation of tubal patency after a medically treated ectopic pregnancy would permit proper counsel of the patient on her fertility options, in order to choose the appropriate method of conception to achieve and accomplish a future pregnancy.
Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group.

PURPOSE The purpose of this study was to evaluate the impact of cisplatin, doxorubicin, and cyclophosphamide (PAC) in patients with advanced thymoma with respect to response rate, duration of remission, and overall survival. PATIENTS AND METHODS Assessable patients with thymoma (n = 29) or thymic carcinoma (n = 1) with metastatic or locally progressive recurrent disease following radiotherapy were treated with intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) with normal saline hydration. Courses were repeated every 3 weeks for a maximum of eight cycles of therapy. RESULTS Toxicity, which was primarily hematologic, was mild, with only one patient developing a fever associated with neutropenia. Three complete responses (CRs) and 12 partial responses (PRs) were observed (CR+PR rate, 50%; 95% confidence interval, 31.3% to 68.7%). Ten patients had stable disease. The median duration of response was 11.8 months (range, 0.9 to 70.5+), the time to treatment failure 18.4 months (range, 0.8 to 91.9+), and median survival time 37.7 months (range, 2 to 91.9+). CONCLUSION This trial demonstrates that objective response rates and prolonged survival can be achieved in patients with advanced thymoma.
Structure of the membrane protein of influenza virus. I. Isolation and characterization of cyanogen bromide cleavage products

After cleavage of the membrane (M) protein of influenza A/WSN virus by using cyanogen bromide (CNBr), six peptide peaks representing approximate molecular weights of 6,000, 4,000, 2,200, 1,600, 1,200, and 1,000 were resolved by gel filtration on BioGel P6. Analysis by thin-layer chromatography indicates that the first, second, fourth, and fifth peaks contain single-peptide components, whereas the third and sixth peaks contain more than one peptide. By using Whatman CM52 ion-exchange chromatography in 5 M urea, four peptides were resolved from the third BioGel P6 peak. The amino acid composition of each of the purified peptides has been determined, and partial sequences were obtained for several peptides. Based on finding a blocked amino terminal residue, the 6,000-dalton fragment appears to contain the amino terminus of the M protein, whereas the carboxy terminal peptide was identified as a 2,000-dalton peptide.