gebhart/patrepeval huggingface dataset:
Effect of Chip Dimension and Substrate Thickness on the Solder JointReliability of Plastic Ball Grid Array Packages (1997)

This paper presents a non‐linear numerical study to investigate the effect of chip dimension and substrate thickness on the solder joint reliability of plastic ball grid array (PBGA) packages. The package under investigation was a 225‐pin full‐grid PBGA assembly. The diagonal cross‐section of the PBGA together with the printed circuit board (PCB) was modelled by plane‐strain elements. A uniform thermal loading was applied and the solder joints were stressed due to the mismatch of coefficient of thermal expansion (CTE) and constructions of the PCB assembly. The effective stress and accumulated plastic strain of solder balls against various chip dimensions and substrate thicknesses were evaluated as an index for the reliability of solder joints. The results of this study are helpful for electronics packaging engineers to optimise the geometry of plastic ball grid array packages.
Postsynaptic Secretion of BDNF and NT-3 from Hippocampal Neurons Depends on Calcium–Calmodulin Kinase II Signaling and Proceeds via Delayed Fusion Pore Opening (2007)

The mammalian neurotrophins (NTs) NGF, BDNF, NT-3, and NT-4 constitute a family of secreted neuronal growth factors. In addition, NTs are implicated in several forms of activity-dependent synaptic plasticity. Although synaptic secretion of NTs has been described, the intracellular signaling cascades that regulate synaptic secretion of NTs are far from being understood. Analysis of NT secretion at the subcellular level is thus required to resolve the role of presynaptic and postsynaptic NT secretion for synaptic plasticity. Here, we transfected cultures of dissociated rat hippocampal neurons with green fluorescent protein-tagged versions of BDNF and NT-3, respectively, and identified NT vesicles at glutamatergic synapses by colocalization with the cotransfected postsynaptic marker PSD-95 (postsynaptic density-95)-DsRed. Depolarization-induced secretion of BDNF and NT-3 was monitored with live cell imaging. Direct postsynaptic depolarization with elevated K+ in the presence of blockers of synaptic transmission allowed us to investigate the signaling cascades that are involved in the postsynaptic NT vesicle secretion process. We show that depolarization-induced postsynaptic NT secretion is elicited by Ca2+ influx, either via L-type voltage-gated calcium channels or via NMDA receptors. Subsequent release of Ca2+ from internal stores via ryanodine receptors is required for the secretion process. Postsynaptic NT secretion is inhibited in the presence of KN-62 ([4(2S)-2-[(5-isoquinolinylsulfonyl)methylamino]-3-oxo-3-(4-phenyl-1-piperazinyl)propyl] phenyl isoquinolinesulfonic acid ester) and KN-93 (N-[2-[[[3-(4-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide), indicating a critical dependence on the activation of alpha-calcium-calmodulin-dependent protein kinase II (CaMKII). The cAMP/protein kinase A (PKA) signaling inhibitor Rp-cAMP-S impaired NT secretion, whereas elevation of intracellular cAMP levels was without effect. Using the Trk inhibitor k252a, we show that NT-induced NT secretion does not contribute to the NT release process at synapses, and BDNF does not induce its own secretion at postsynaptic sites. Release experiments in the presence of the fluorescence quencher bromphenol blue provide evidence for asynchronous and prolonged fusion pore opening of NT vesicles during secretion. Because fusion pore opening is fast compared with compound release, the speed of NT release seems to be limited by diffusion of NTs out of the vesicle. Together, our results reveal a strong dependence of activity-dependent postsynaptic NT secretion on Ca2+ influx, Ca2+ release from internal stores, activation of CaMKII, and intact PKA signaling, whereas Trk signaling and activation of Na+ channels is not required.
mda- 7 (IL-24) mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK (2002)

Subtraction hybridization identified melanoma differentiation-associated gene-7 (mda-7) as a gene induced during terminal differentiation in human melanoma cells. On the basis of structure, chromosomal localization and cytokine-like properties, mda-7 is classified as IL-24. Administration of mda-7/IL-24 by means of a replication-incompetent adenovirus (Ad.mda-7) induces apoptosis selectively in diverse human cancer cells without inducing harmful effects in normal fibroblast or epithelial cells. The present studies investigated the mechanism underlying this differential apoptotic effect. Infection of melanoma cells, but not normal immortal melanocytes, with Ad.mda-7 induced a time- and dose-dependent increase in expression, mRNA and protein, of a family of growth arrest and DNA damage (GADD)-inducible genes, which correlated with induction of apoptosis. Among the members of the GADD family of genes, GADD153, GADD45 alpha, and GADD34 displayed marked, and GADD45 gamma showed minimal induction. Treatment of melanoma cells with SB203580, a selective inhibitor of the p38 mitogen-activated protein kinase (MAPK) pathway, effectively inhibited Ad.mda-7-induced apoptosis. Additional support for an involvement of the p38 MAPK pathway in Ad.mda-7-mediated apoptosis was documented by using an adenovirus expressing a dominant negative mutant of p38 MAPK. Infection with Ad.mda-7 increased the phosphorylation of p38 MAPK and heat shock protein 27 in melanoma cells but not in normal immortal melanocytes. In addition, SB203580 effectively inhibited Ad.mda-7-mediated induction of the GADD family of genes in a time- and dose-dependent manner, and it effectively blocked Ad.mda-7-mediated down-regulation of the antiapoptotic protein BCL-2. Inhibition of GADD genes by an antisense approach either alone or in combination also effectively blocked Ad.mda-7-induced apoptosis in melanoma cells. These results support the hypothesis that Ad.mda-7 mediates induction of the GADD family of genes by means of the p38 MAPK pathway, thereby resulting in the selective induction of apoptosis in human melanoma cells.
The Competence of Maize Shoot Meristems for Integrative Transformation and Inherited Expression of Transgenes (1996)

We have developed a novel and reproducible system for recovery of fertile transgenic maize (Zea mays L.) plants. The transformation was performed using microprojectile bombardment of cultured shoot apices of maize with a plasmid carrying two linked genes, the Streptomyces hygroscopicus phosphinothricin acetyltransferase gene (bar) and the potato proteinase inhibitor II gene, either alone or in combination with another plasmid containing the 5[prime] region of the rice actin 1 gene fused to the Escherichia coli [beta]-glucuronidase gene (gus). Bombarded shoot apices were subsequently multiplied and selected under 3 to 5 mg/L glufosinate ammonium. Co-transformation frequency was 100% (146/146) for linked genes and 80% (41/51) for unlinked genes. Co-expression frequency of the bar and gus genes was 57% (29/51). The co-integration, co-inheritance, and co-expression of bar, the potato proteinase inhibitor II gene, and gus in transgenic R0, R1, and R2 plants were confirmed. Localized expression of the actin 1-GUS protein in the R0 and R1 plants was extensively analyzed by histochemical and fluorometric assays.
Activating transcription factor-2 DNA-binding activity is stimulated by phosphorylation catalyzed by p42 and p54 microtubule-associated protein kinases. (1992)

Recent studies have detailed the ability of activating transcription factor-2 (ATF-2) to mediate adenoviral E1a stimulation of gene expression; however, an endogenous regulator for the transcriptional activity of this protein has not been described. To characterize the regulation of ATF-2 activity, we have expressed full-length and truncated peptides corresponding to various regions of the ATF-2 protein in bacteria and the baculovirus insect cell system. Bacterially expressed truncated (350-505) but not full-length ATF-2, was able to bind a consensus cAMP response element-containing oligonucleotide, suggesting the N-terminal moiety may serve as a negative regulator of DNA-binding activity. In contrast, the full-length ATF-2 protein expressed in Spodoptera frugiperda (Sf9) cells using a recombinant baculovirus was fully competent to bind DNA. Protein phosphatase 2A reversed the DNA-binding activity by dephosphorylating the ATF-2 polypeptide. Microtubule-associated protein kinase catalyzed the phosphorylation and stimulated the DNA-binding activity of bacterially expressed full-length ATF-2. Phosphopeptide mapping of phosphorylated ATF-2 proteins identified a single peptide in the N-terminal moiety of ATF-2 phosphorylated by p42 or p54 microtubule-associated protein kinase. Therefore, we propose that phosphorylation of this regulatory site is sufficient to induce an allosteric structural change in the ATF-2 protein, which allows dimerization and subsequent DNA binding.
Characterization of Recombinant Human Fibroblast Growth Factor (FGF)-10 Reveals Functional Similarities with Keratinocyte Growth Factor (FGF-7) (1998)

A newly identified member of the fibroblast growth factor (FGF) family, designated FGF-10, is expressed during development and preferentially in adult lung. The predicted FGF-10 protein is most related to keratinocyte growth factor (KGF, or FGF-7). The latter is unique among FGFs in that it binds and signals only through the FGF receptor (FGFR2b) isoform KGF receptor (KGFR) expressed specifically by epithelial cells. In order to examine the biological and biochemical properties of human FGF-10, we isolated the cDNA and expressed its encoded protein in bacteria. The recombinant protein (rFGF-10) was a potent mitogen for Balb/MK mouse epidermal keratinocytes with activity detectable at 0.1 nM and maximal at around 5 nM. Within this concentration range, FGF-10 did not stimulate DNA synthesis in NIH/3T3 mouse fibroblasts. rFGF-10 bound the KGFR with high affinity comparable to that of KGF, and did not bind detectably to either the FGFR1c (Flg) or FGFR2c (Bek) receptor isoforms. The mitogenic activity of FGF-10 could be distinguished from that of KGF by its different sensitivity to heparin and lack of neutralization by a KGF monoclonal antibody. These results indicate that FGF-10 and KGF have similar receptor binding properties and target cell specificities, but are differentially regulated by components of the extracellular matrix.
Cache-oblivious ray reordering (2010)

We present a cache-oblivious ray reordering method for ray tracing. Many global illumination methods such as path tracing and photon mapping use ray tracing and generate lots of rays to simulate various realistic visual effects. However, these rays tend to be very incoherent and show lower cache utilizations during ray tracing of models. In order to address this problem and improve the ray coherence, we propose a novel Hit Point Heuristic (HPH) to compute a coherent ordering of rays. The HPH uses the hit points between rays and the scene as a ray reordering measure. We reorder rays by using a space-filling curve based on their hit points. Since a hit point of a ray is available only after performing the ray intersection test with the scene, we compute an approximate hit point for the ray by performing an intersection test between the ray and simplified representations of the original models. Our method is a highly modular approach, since our reordering method is decoupled from other components of common ray tracing systems. We apply our method to photon mapping and path tracing and achieve more than an order of magnitude performance improvement for massive models that cannot fit into main memory, compared to rendering without reordering rays. Also, our method shows a performance improvement even for ray tracing small models that can fit into main memory. This performance improvement for small and massive models is caused by reducing cache misses occurring between different memory levels including the L1/L2 caches, main memory, and disk. This result demonstrates the cache-oblivious nature of our method, which works for various kinds of cache parameters. Because of the cache-obliviousness and the high modularity, our method can be widely applied to many existing ray tracing systems and show performance improvements with various models and machines that have different cache parameters.
Rac1 activation inhibits E-cadherin-mediated adherens junctions via binding to IQGAP1 in pancreatic carcinoma cells (2009)

These results indicate that active Rac1 destabilises E-cadherin-mediated cell-cell adhesion in pancreatic carcinoma cells by interacting with IQGAP1 which is associated with a disassembly of E-cadherin-mediated adherens junctions. Inhibition of Rac1 activity induced increased E-cadherin-mediated cellular adhesion.
Identification of an iron-regulated virulence determinant in Vibrio cholerae, using TnphoA mutagenesis (1990)

Several virulence determinants of bacteria are regulated by the concentration of iron in the medium, with increased expression occurring under low-iron conditions. Iron-regulated virulence factors have not been previously described in Vibrio cholerae. We used the transposon vector Tn5 IS50L::phoA (TnphoA) to obtain insertion mutations in iron-regulated genes of V. cholerae 0395. One strain, carrying an insertion mutation in iron-regulated gene irgA, had reduced virulence in an animal model and had lost the 77-kilodalton major iron-regulated outer membrane protein. The 50% lethal dose of this mutant strain (MBG40) in suckling mice was 3 x 10(5) bacteria compared with 4 x 10(3) bacteria for 0395 wild type. In an in vivo competition assay, the wild-type strain out competed the mutant almost 10-fold, suggesting a possible colonization defect in MBG40. The in vitro competitive index and in vitro growth curves in low- and high-iron media showed that the mutant strain had no discernable growth defect. These data suggest that the 77-kilodalton iron-regulated outer membrane protein may play a role in the pathogenesis of V. cholerae infection. It is not yet clear whether the reduction of virulence in MBG40, as assessed by 50% lethal dose analysis, is explained by a colonization defect or whether it relates to another defect associated with loss of the IrgA protein.
A New Strategy to Induce γ-Turns:  Peptides Composed of Alternating α-Aminoxy Acids and α-Amino Acids (2003)

It is known that the seven-membered-ring intramolecular hydrogen bond (gamma-turn) is seldom formed in naturally occurring peptides composed of alpha-amino acids. Here we report a new strategy to induce gamma-turns in short linear peptides. We designed and synthesized several peptides (1-5) containing alternating alpha-l-aminoxy acids and alpha-d-amino acids. 1H NMR studies revealed that the gamma-turn could be initiated by the following N-O turn, an eight-membered-ring intramolecular hydrogen bond induced by an alpha-aminoxy acid. Moreover, NOESY and CD studies suggested peptides 4 and 5 form a novel secondary structure, a mixed 7-8 helix. Theoretical calculations on several di-, tri-, and tetrapeptide models provided strong support to the above conclusions.
Polymorphism of HIV Type 1 Gag p7/p1 and p1/p6 Cleavage Sites: Clinical Significance and Implications for Resistance to Protease Inhibitors (2000)

Amino acid substitutions at HIV-1 Gag p7/p1 and p1/p6 cleavage sites may be selected under antiretroviral pressure or represent natural polymorphisms. Whether changes are associated with specific protease (PR) mutation patterns and different clinical evolution has not been investigated. p7/p1 and p1/p6 cleavage site sequences from sera from 110 patients infected with HIV-1 were compared by regression analysis, using clinical, laboratory, and sequence variables, and the evolution of CD4+ cell counts and viral load over time. Sixteen of 35 (46%) individuals naive to PR inhibitors (PIs), and 49 of 75 (65%) receiving PI-containing regimens had a p7/p1 and/or p1/p6 cleavage site polymorphism (p = 0.06). A431V and/or L449F were present exclusively among individuals failing PI treatment (17 of 75 [23%] and 3 of 75 [3%], respectively). There was a significant association between A431V and PR M46I,L (OR 13.7; 95% CI 4.2-44.3) and V82A,F,T (OR 8.8; 95% CI 2.7-27.8). Natural polymorphism P453L was strongly associated with the selection of PR I84V (OR 49.5; 95% CI 12-212) and selected against V82 mutation (OR 0.15; 95% CI 0.02-1.2). After a median followup of 15 months, no polymorphism was associated with parameters of disease progression among individuals failing treatment. Only a limited set of amino acid substitutions can be tolerated at p7/p1 and p1/p6 cleavage sites. A431V is selected in association with specific PR inhibitor mutations. Natural polymorphism P453L might direct the PR resistance pathway through I84V instead of V82 mutation. No short-term clinical impact of cleavage site substitutions was documented.
Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. (1992)

The "high-risk" human papillomavirus types 16 (HPV-16) and 18 (HPV-18) have been etiologically implicated in the majority of human cervical carcinomas. In these cancers, the viral DNAs are often integrated into the host genome so that expression of the E1 and the E2 genes is lost, suggesting that disruption of these regulatory genes plays an important role in carcinogenic progression. Previous studies defining the viral genes affecting HPV-16 transformation functions have used the "prototype" viral genome, which was cloned from a human cervical carcinoma and later discovered to harbor a mutation in the E1 gene. In this study, we have corrected this mutation and have evaluated the effect of mutations of either the E1 or the E2 gene on the efficiency of HPV-16 immortalization of human keratinocytes. Mutation of either the E1 gene or the E2 gene in the background of a "wild-type" HPV-16 genome markedly increased immortalization capacity. Mutations were also generated in the E2-binding sites located upstream of the P97 promoter, which directs synthesis of the viral E6 and E7 transforming genes. E2 negatively regulates the P97 promoter through binding at adjacent sites. Surprisingly, the mutation of these sites only partially relieved the negative effect of E2 on viral immortalization, implicating additional mechanisms in the E2 repression of viral immortalization functions. Our results provide genetic evidence that the E1 and E2 gene products each can repress HPV-16 immortalization and support the hypothesis that a selective growth advantage is provided by integration of the viral genome in a manner that causes the loss of expression of either E1 or E2.
Long term survival of allografted muscle precursor cells following a limited period of treatment with cyclosporin A. (1984)

Previous work (Watt et al., 1982) has shown that, in the mouse, skeletal muscle can be transplanted successfully in the form of a suspension of it's mononucleate precursors. Eventual therapeutic application of this technique by the implantation of precursor cells derived from normal muscle into myopathic individuals would require a means of preventing allograft rejection applicable to man. We have therefore investigated the use of the drug cyclosporin A (CyA) as a means of prolonging the survival in mice of allografts of mononucleate muscle cells made into a region of regenerating host muscle. We have administered CyA to the hosts at doses of either 75 or 150 mg/kg body weight/day for 42 days from the day of grafting. By using isoenzyme allotypes as markers of host and donor tissues, we have shown that allografted mononucleate cells become incorporated in host muscle fibres and that the mosaic host/donor muscle fibres so formed survive for as long as we continued the experiment, a maximum of 107 days after grafting, or 65 days after the end of CyA treatment.
Synthesis of Monodisperse FeAu Nanoparticles with Tunable Magnetic and Optical Properties (2007)

Abstract Monodisperse FeAu nanoparticles can be synthesized via the reduction of gold acetate by 1,2‐hexadecanediol and the thermal decomposition of iron pentacarbonyl in the presence of the stabilizers oleic acid and oleylamine. The effects of composition, reaction time, and reaction temperature on their size, structure, and optical and magnetic properties are studied. It is found that the incorporation of Au into Fe nanoparticles leads to a structural change from body‐centered cubic (bcc) to face‐centered cubic (fcc). The size of the particles decreases with increasing reaction time and temperature because of atom rearrangement, and varies with the Au/Fe molar ratio as a result of the faster reduction rate of gold acetate compared with the decomposition rate of iron pentacarbonyl and the associated changes in nucleation and growth processes. The resultant FeAu nanoparticles possess the optical properties of Au nanoparticles and the magnetic properties of Fe nanoparticles. Their characteristic absorption bands, in the visible light range, become broader with decreasing Au/Fe molar ratio or increasing reaction time and temperature. Also, they are red‐shifted with decreasing the Au content and blue‐shifted with increasing reaction time. In addition, the particles are nearly superparamagnetic. With the increase in the Au/Fe molar ratio, their blocking temperature and coercivity increase while the saturation magnetization and remnant magnetization decrease. They can be self‐assembled into parallel stripes in the direction of an applied magnetic field.
STAT3: A Central Mediator of Pulmonary Fibrosis? (2012)

Pulmonary fibrosis is a devastating, relentlessly progressive, and lethal disease. There is a significant unmet need for effective treatment since currently no FDA-approved therapies exist. Current thinking suggests that idiopathic pulmonary fibrosis (IPF) is initiated by pathways similar to normal wound healing, but relentless fibrosis occurs secondary to absent or defective inhibitory mechanisms that normally terminate wound healing. The heterogeneous pathological presentation of fibrosis suggests that the anatomic location and origin of fibroblasts and other cells might be critical for their phenotype and function and will impact on strategies to prevent or treat fibrotic lung diseases. This review summarizes our current understanding of the pathobiology of IPF, with a specific focus on the role of STAT3 in regulating cellular responses that may contribute to or inhibit pro-fibrotic processes. An improved understanding of the complex cell-type specific roles that this transcription factor plays in normal lung and in fibrosis is required to determine its suitability as an effective therapeutic target.