gebhart/patrepeval huggingface dataset:
Immune Response: The Key to Bone Resorption in Periodontal Disease (2005)

Periodontal disease infection with oral biofilm microorganisms initiates host immune response and signs of periodontitis, including bone resorption. This review delineates some mechanisms underlying the host immune response in periodontal infection and alveolar bone resorption. Activated T lymphocytes have been historically implicated in experimental periodontal bone resorption. An experimental rat adoptive transfer/gingival challenge periodontal disease model has been demonstrated to require antigen-specific T lymphocytes and gingival instillation of antigen and LPS for bone resorption. Interference with costimulatory interactions between T cells and antigen-presenting cells abrogated bone resorption, further emphasizing the significance of immune response in periodontal disease. Receptor activator of nuclear factor kappaB ligand (RANKL), a critical osteoclast differentiation factor, is expressed on T lymphocytes in human periodontal disease as determined by immunohistochemical and confocal microscopic analyses. Interference with RANKL by systemic administration of osteoprotegerin (OPG), the decoy receptor for (and inhibitor of) RANKL, resulted in abrogation of periodontal bone resorption in the rat model. This finding indicated that T cell-mediated bone resorption is RANKL-dependent. In additional experiments, treatment of T cell-transferred rats with kaliotoxin (a scorpion venom potassium channel inhibitor) resulted in decreases in T-cell RANKL expression, diminished induction of RANKL-dependent osteoclastogenesis, and abrogation of bone resorption, implicating an important role of immune response/RANKL expression in osteoclastogenesis/bone resorption. In other experiments, adoptive transfer of antigen-specific, RANKL-expressing B cells, and infection with the antigen-bearing Actinobaccillus actinomycetemcomitans gave rise to periodontal bone resorption, indicating that B cells also have the capacity to mediate bone resorption, probably via RANKL expression. In humans, prominent T lymphocytes have been identified in periodontal disease, and diseased tissues showed elevated RANKL mRNA expression, as well as decreased OPG mRNA expression. Mononuclear cells from periodontal lesions involving T cells and B cells of patients induced osteoclastogenesis in vitro. In summary, a biofilm interface initiates immune cell infiltration, stimulating osteoclastogenesis/bone resorption in periodontal disease. This resorption can be ameliorated by inhibition of RANKL activity or by diminishing immune cell stimulation. These two procedures, if localized, have the potential to lead to the prevention or therapeutic management of periodontal disease and therefore require further study.
Microglia/macrophages promote glioma progression (2010)

Gliomas are highly aggressive and accompanied by numerous microglia/macrophages (MG/MP) in and about the tumor. Little is known about what MG/MP do in this setting, or whether modulating MG/MP activation might affect glioma progression. Here, we used a glioma-microglia in culture system to establish the effects the tumor and microglia have on each other. We assessed glioma progression in vivo after MG/MP ablation or in the setting of exaggerated MG/MP activation. We show that glioma cells activate microglia but inhibit their phagocytic activities. Local ablation of MG/MP in vivo decreased tumor size and improved survival curves. Conversely, pharmacological activation of MG/MP increased glioma size through stimulating tumor proliferation and inhibiting apoptosis. In agreement with recent reports, expression of the chemokine CCL21 is enhanced after MG/MP activation and correlates with tumor growth. Taken together, our findings demonstrate that inhibition of MG/MP activation may constitute a new and effective contribution towards suppressing glioma proliferation.
Mitochondria and Cardiovascular Aging (2012)

Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and in cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity, and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (eg, renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics, and exercise training.
A 3-D Packaging Technology with Highly-Parallel Memory/Logic Interconnect (2009)

A three-dimensional semiconductor package structure with inter-chip connections was developed for broadband data transfer and low latency electrical communication between a high-capacity memory and a logic device interconnected by a feedthrough interposer (FTI) featuring a 10µm scale fine-wiring pattern and ultra-fine-pitch through vias. This technology features co-existence of the wide-band memory accessibility of a system-on-chip (SoC) and the capability of memory capacity increasing of a system-in-package (SiP) that is made possible by the individual fabrication of memory and logic on independent chips. This technology can improve performance due to memory band widening and a reduction in the power consumed in inter-chip communications. This paper describes the concept, structure, process, and experimental results of prototypes of this package, called SMAFTI (SMAart chip connection with FeedThrough Interposer). This paper also reports the results of the fundamental reliability test of this novel inter-chip connection structure and board-level interconnectivity tests.
THIP, a Hypnotic and Antinociceptive Drug, Enhances an Extrasynaptic GABAA Receptor-mediated Conductance in Mouse Neocortex (2005)

THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a selective GABA(A) receptor agonist with a preference for delta-subunit containing GABA(A) receptors. THIP is currently being tested in human trials for its hypnotic effects, displaying advantageous tolerance and addiction properties. Since its cellular actions in the neocortex are uncertain, we studied the effects of THIP on neurons in slices of frontoparietal neocortex of 13- to 19-day-old (P13-19) mice. Using whole-cell patch-clamp recordings, we found that the clinically relevant THIP concentration of 1 muM induced a robust tonic GABA(A)-mediated current in layer 2/3 neurons. In comparison, only a minute tonic current was induced by mimicking in vivo endogenous GABA levels. Miniature IPSCs were not affected by 1 muM THIP suggesting an extrasynaptic site of action. The EC(50) for THIP was 44 muM. In accordance with the stronger expression of delta-containing receptors in superficial neocortical layers, THIP induced a 44% larger tonic current in layer 2/3 than in layer 5 neurons. Finally, monitoring spontaneously active neocortical neurons, THIP caused an overall depression of inhibitory activity, while enhancing excitatory activity prominently. Our studies suggest that THIP activates an extrasynaptic GABA(A) receptor-mediated conductance in the neocortex, which may alter the cortical network activity.
Facile and Scalable Synthesis of Tailored Silica “Nanorattle” Structures (2009)

Silica “nanorattles” are fabricated by means of selective etching of ingeniously designed organic–inorganic hybrid silica spheres with a three-layer “sandwich” structure. The size (95–645 nm), shell thickness, and core diameter of the monodisperse nanorattles can be precisely controlled, even in gram-scale production. This method is also shown to be promising for development as a general method for synthesis of rattle-type functional nanomaterials.
Microglia ablation alleviates myelin-associated catatonic signs in mice (2017)

The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression of the structural myelin protein CNP is associated with catatonic signs in an age-dependent manner, pointing to the involvement of myelin-producing oligodendrocytes. Here, we showed that the underlying cause of catatonic signs is the low-grade inflammation of white matter tracts, which marks a final common pathway in Cnp-deficient and other mutant mice with minor myelin abnormalities. The inhibitor of CSF1 receptor kinase signaling PLX5622 depleted microglia and alleviated the catatonic symptoms of Cnp mutants. Thus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously unexplained mental condition. We observed a very high (25%) prevalence of individuals with catatonic signs in a deeply phenotyped schizophrenia sample (n = 1095). Additionally, we found the loss-of-function allele of a myelin-specific gene (CNP rs2070106-AA) associated with catatonia in 2 independent schizophrenia cohorts and also associated with white matter hyperintensities in a general population sample. Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities.
Difluorboryl‐Komplexe von Di‐ und Tripyrrylmethenen (1968)

Abstract Di‐ und Tripyrrylmethene bilden mit Bortrifluorid in Gegenwart von tert. Basen stabile, gelbe bis rote Difluorboryl‐Komplexe 1–9 , die bei Anwesenheit negativer Substituenten Alkalisalze ( z. B. 12–14) bilden können. Alle Dipyrrylmethen/Bor‐Komplexe sind durch intensive Fluoreszenz ausgezeichnet. Ebenso wie die Salzbildung ist der Verlauf der katalytischen Hydrierung (3 → 16, 7 → 17) von der Substitution der Pyrrol‐Kerne abhängig. – Auch Aluminium bildet stark fluoreszierende Komplexe mit Dipyrrylmethenen, die aber wegen ihrer extremen Wasserempfindlichkeit noch nicht näher untersucht wurden. – Das Tripyrrylmethen 11 wurde durch Reaktion eines Pyrrol‐Derivates mit Oxalylchlorid erhalten.
Tunable, continuous-wave, ultraviolet source based on intracavity sum-frequency-generation in an optical parametric oscillator using BiB_3O_6 (2013)

We report a continuous-wave (cw) source of tunable radiation across 333-345 nm in the ultraviolet (UV) using bismuth triborate, BiB₃O₆ (BIBO) as the nonlinear gain material. The source is based on internal sum-frequency-generation (SFG) in a cw singly-resonant optical parametric oscillator (OPO) pumped at 532 nm. The compact tunable source employs a 30-mm-long MgO:sPPLT crystal as the OPO gain medium and a 5-mm-long BIBO crystal for intracavity SFG of the signal and pump, providing up to 21.6 mW of UV power at 339.7 nm, with >15 mW over 64% of the SFG tuning range. The cw OPO is also tunable across 1158-1312 nm in the idler, delivering as much as 1.7 W at 1247 nm, with >1W over 65% of the tuning range. The UV output at maximum power exhibits passive power stability better than 3.4% rms and frequency stability of 193 GHz over more than one minute.
Disinfection of Hospital Rooms Contaminated With Vancomycin-Resistant Entemcocms faecium (1998)

Sixteen percent of hospital room surfaces remained colonized by vancomycin-resistant enterococci (VRE) after routine terminal disinfection. Disinfection with a new "bucket method" resulted in uniformly negative cultures. Conventional cleaning took an average of 2.8 disinfections to eradicate VRE from a hospital room, while only one cleaning was required with the bucket method.
The a-factor pheromone of Saccharomyces cerevisiae is essential for mating. (1988)

The Saccharomyces cerevisiae pheromone a-factor is produced by a cells and interacts with alpha cells to cause cell cycle arrest and other physiological responses associated with mating. Two a-factor structural genes, MFA1 and MFA2, have been previously cloned with synthetic probes based on the a-factor amino acid sequence (A. Brake, C. Brenner, R. Najarian, P. Laybourn, and J. Merryweather, cited in M.-J. Gething [ed.], Protein transport and secretion, 1985). We have examined the function of these genes in a-factor production and mating by construction and analysis of chromosomal null mutations. mfa1 and mfa2 single mutants each exhibited approximately half the wild-type level of a-factor activity and were proficient in mating, whereas the mfa1 mfa2 double mutant produced no a-factor and was unable to mate. These results demonstrate that both genes are functional, that each gene makes an equivalent contribution to the a-factor activity and mating capacity of a cells, and that a-factor plays an essential role in mating. Strikingly, exogenous a-factor did not alleviate the mating defect of the double mutant, suggesting that an a cell must be producing a-factor to be an effective mating partner.
Molecular Neurobiology of Addiction (2001)

Addiction can be viewed as a form of drug-induced neural plasticity. One of the best established molecular mechanisms of addiction is the upregulation of the cAMP second messenger pathway, which occurs in many neuronal cell types in response to chronic administration of opiates or other drugs of abuse. This upregulation and the resulting activation of the transcription factor CREB appear to mediate aspects of tolerance and dependence. In contrast, induction of another transcription factor, termed delta FosB, exerts the opposite effect and may contribute to sensitized responses to drug exposure. Knowledge of these mechanisms could lead to more effective treatments for addictive disorders.
Production of Functional Glucagon-Secreting α-Cells From Human Embryonic Stem Cells (2010)

These results indicate that fully differentiated pancreatic endocrine cells can be created via stepwise differentiation of hES cells. These cells may serve as a useful screening tool for the identification of compounds that modulate glucagon secretion as well as those that promote the transdifferentiation of α-cells to β-cells.
Implication of high dynamic range and wide color gamut content distribution (2015)

High Dynamic Range (HDR) and Wider Color Gamut (WCG) content represents a greater range of luminance levels and a more complete reproduction of colors found in real-world scenes. The current video distribution environments deliver Standard Dynamic Range (SDR) signal. Therefore, there might be some significant implication on today's end-to-end ecosystem from content creation to distribution and finally to consumption. For SDR content, the common practice is to apply compression on Y'CbCr 4:2:0 using gamma transfer function and non-constant luminance 4:2:0 chroma subsampling. For HDR and WCG content, it is desirable to examine if such signal format still works well for compression, and it is interesting to know if the overall system performance can be further improved by exploring different signal formats and processing workflows. In this paper, we will provide some of our insight into those problems.
The Design, Synthesis and Potential Utility of Fluorescence Probes that Target DFG‐out Conformation of p38α for High Throughput Screening Binding Assay (2009)

The design, synthesis and utility of fluorescence probes that bind to the DFG-out conformation of p38alpha kinase are described. Probes that demonstrate good affinity for p38alpha, have been identified and one of the probes, PF-04438255, has been successfully used in an high throughput screening (HTS) assay to identify two novel non-classical p38alpha inhibitors. In addition, a cascade activity assay was utilized to validate the selective binding of these non-classical kinase inhibitors to the unactive form of the enzyme.
New monoclonal antibodies specific for human sarcomas (1986)

Monoclonal antibodies (MAbs) against sarcoma-associated cell membrane antigens were prepared by immunizing BALB/c mice with tumor cells from a human osteosarcoma, TPX, grown as a xenograft in athymic BALB/c nude mice. Spleen cells from immunized mice were hybridized with X-63 Ag. 8.653 mouse myeloma cells which yielded 260 growing hybridomas. Seven of these produced antibodies that bound to TPX cells and to cells from another osteosarcoma, but not to autologous skin fibroblasts. MAbs from 2 (TP-1 and TP-3) of these 7 clones did not cross-react with non-sarcomatous tumor cells or peripheral blood lymphocytes. Immunohistochemical studies on frozen tissue sections showed that the TP-1 (IgG-2a) and TP-3 (IgG-2b) antibodies had characteristic and identical specificity profiles. Binding of TP-1 (TP-3) was demonstrated to 15/15 (15/15) osteosarcomas, 3/3 (2/2) synovial sarcomas, 7/9 (6/8) malignant fibrous histiocytomas, 2/2 (1/1) malignant hemangiopericytomas, 1/2 (1/2) chondrosarcomas and 3/6 (1/3) unclassified sarcomas. The antibodies did not bind to any of 16 sarcomas belonging to other histological subtypes, including liposarcomas and leio- and rhabdomyosarcomas. Moreover, they failed to bind to sections of 66 different non-sarcomatous malignancies, or to any of a range of normal adult and fetal tissues, although some weak staining of proximal kidney tubules was seen. The restricted specificity of these antibodies to some major subtypes of human sarcomas makes them promising tools for identification and subclassification of sarcomas.
Low-resistance ohmic contacts on p-type GaN using Ni/Pd/Au metallization (2000)

In this letter, a low-resistance ohmic contact on p-type GaN using an alloy of Ni/Pd/Au is reported. The Mg doped p-type GaN samples were grown by metalorganic chemical vapor deposition with a carrier concentration of 4.1×1017 cm−3. The as-grown Mg doped samples were deposited with Ni (20 nm)/Pd (20 nm)/Au (100 nm) and then annealed in air, nitrogen, and oxygen ambient conditions at different annealing temperatures ranging from 350 to 650 °C. Linear I–V ohmic characteristics were observed with specific resistance as low as 1.0×10−4 Ω cm2 for the samples annealed in oxygen atmosphere. Similar contact metal composition was also deposited on Be-implanted p-type GaN samples with a carrier density of 8.1×1019 cm−3. Without further annealing process, the samples show good ohmic contact with a lowest specific resistance of 4.5×10−6 Ω cm2.
CNVkit: Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing (2016)

Germline copy number variants (CNVs) and somatic copy number alterations (SCNAs) are of significant importance in syndromic conditions and cancer. Massively parallel sequencing is increasingly used to infer copy number information from variations in the read depth in sequencing data. However, this approach has limitations in the case of targeted re-sequencing, which leaves gaps in coverage between the regions chosen for enrichment and introduces biases related to the efficiency of target capture and library preparation. We present a method for copy number detection, implemented in the software package CNVkit, that uses both the targeted reads and the nonspecifically captured off-target reads to infer copy number evenly across the genome. This combination achieves both exon-level resolution in targeted regions and sufficient resolution in the larger intronic and intergenic regions to identify copy number changes. In particular, we successfully inferred copy number at equivalent to 100-kilobase resolution genome-wide from a platform targeting as few as 293 genes. After normalizing read counts to a pooled reference, we evaluated and corrected for three sources of bias that explain most of the extraneous variability in the sequencing read depth: GC content, target footprint size and spacing, and repetitive sequences. We compared the performance of CNVkit to copy number changes identified by array comparative genomic hybridization. We packaged the components of CNVkit so that it is straightforward to use and provides visualizations, detailed reporting of significant features, and export options for integration into existing analysis pipelines. CNVkit is freely available from https://github.com/etal/cnvkit.
Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches (2006)

The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between high mRNA levels of G250/CA9 and longer overall survival (P = .022), a similar trend with high mRNA levels of PRAME (P = .103), and a hint for RHAMM/HMMR. In contrast, for other TAAs like WT1, TERT, PRTN3, BCL2, and LAMR1, we found no correlation with clinical outcome. High expression of at least 1 of the 3 TAAs, RHAMM/HMMR, PRAME, or G250/CA9, provided the strongest favorable prognostic effect (P = .005). Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease (P < .001). Furthermore, we could demonstrate specific lysis of T2 cells presenting these epitope peptides. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML.