gebhart/patrepeval huggingface dataset:
Composite structure of auxin response elements. (1995)

The auxin-responsive soybean GH3 gene promoter is composed of multiple auxin response elements (AuxREs), and each AuxRE contributes incrementally to the strong auxin inducibility to the promoter. Two independent AuxREs of 25 bp (D1) and 32 bp (D4) contain the sequence TGTCTC. Results presented here show that the TGTCTC element in D1 and D4 is required but not sufficient for auxin inducibility in carrot protoplast transient expression assays. Additional nucleotides upstream of TGTCTC are also required for auxin inducibility. These upstream sequences showed constitutive activity and no auxin inducibility when part or all of the TGTCTC element was mutated or deleted. In D1, the constitutive element overlaps the 5' portion of TGTCTC; in D4, the constitutive element is separated from TGTCTC. An 11-bp element in D1, CCTCGTGTCTC, conferred auxin inducibility to a minimal cauliflower mosaic virus 35S promoter in transgenic tobacco seedlings as well as in carrot protoplasts (i.e., transient expression assays). Both constitutive elements bound specifically to plant nuclear proteins, and the constitutive element in D1 bound to a recombinant soybean basic leucine zipper transcription factor with G-box specificity. To demonstrate further the composite nature of AuxREs and the ability of the TGTCTC element to confer auxin inducibility, we created a novel AuxRE by placing a yeast GAL4 DNA binding site adjacent to the TGTCTC element. Expression of a GAL4-c-Rel transactivator in the presence of this novel AuxRE resulted in auxin-inducible expression. Our results indicate that at least some AuxREs have a composite structure consisting of a constitutive element adjacent to a conserved TGTCTC element that confers auxin inducibility.
Control of the critical dimensions and line edge roughness with pre-organized block copolymer pixelated photoresists (2009)

Sphere-forming polystyrene-block-poly(t-butyl acrylate) (PS-b-PtBA) diblock copolymer with catalytic amounts of photo-acid generator (PAG) formulated a pixelated photoresist. In thin films with single-sphere thickness, hexagonal arrays of spheres (∼20 nm diameter on a 40 nm pitch) of PS within a matrix of PAG segregated in PtBA was obtained through solvent annealing. Upon exposure and post-exposure baking, the soluble PtBA matrix was converted to insoluble poly(acrylic acid), such that a negative pattern could be formed in the chlorobenzene developer. The concept of pixelation was demonstrated by exposing line and space patterns with increasing widths. In contrast to the width of the exposure fields that increased monotonically, the widths of the pixelated resist structures after development were quantized with respect to an integer number of rows of spheres. Furthermore, line edge roughness could be correlated with the size of each pixel (diameter of spherical domain).
Matrix adhesion characteristics of corneal myofibroblasts. (1999)

Differentiation of corneal fibroblasts into myofibroblasts is associated with characteristics that would indicate that the latter have a special role in wound closure. The increase in focal and cell adhesion molecules that accompanies smooth muscle-specific actin expression provides the basis for the myofibroblasts' enhanced cell-fibronectin and cell-cell adhesion.
Integrated Optical Displacement Detection and Electrostatic Actuation for Directional Optical Microphones With Micromachined Biomimetic Diaphragms (2009)

In this paper, integration and packaging of directional biomimetic microphones using a diffraction-based optical displacement detection method is described. The optical detection method senses the displacement of the microphone diaphragm by monitoring the change in the intensity of a diffracted laser beam. A detailed optical model of the integrated optical detection scheme is developed and used to guide the package design. Measurement results with microphone packages suitable for hearing aid and acoustic measurement systems show that the noise and sensitivity performances of these small-sized microphones are comparable with commercial miniature directional microphones. These microphones incorporate integrated electrostatic actuators which can be used for active feedback control. This capability is also demonstrated to improve the frequency response of the microphone without degrading its noise performance.
Interaction between dental metals and antioxidants, assessed by cytotoxicity assay and ESR spectroscopy. (2003)

Among dental metals, copper showed the highest cytotoxicity against human oral squamous cell carcinoma and human submandibular gland carcinoma cells, followed by palladium-alloy, gold and silver. Normal human cells (gingival fibroblast, pulp cells, periodontal ligament fibroblast) were relatively resistant to these metals. The palladium-alloy failed to induce internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemic HL-60 cells. The cytotoxic activity of the palladium-alloy was significantly reduced by a non-cytotoxic concentration of N-acetyl-L-cysteine, or more efficiently by sodium ascorbate. However, higher concentrations of sodium ascorbate enhanced the cytotoxic activity of palladium-alloy. ESR spectroscopy showed that the palladium-alloy enhanced the intensity of ascorbate radical, suggesting the possible interaction between metals and antioxidants. All metals, except copper, did not significantly affect the generation of superoxide anion (by hypoxanthine-xanthine oxidase reaction), hydroxyl radical (by Fenton reaction) and nitric oxide (from NOC-7 in the presence of C-PTIO). These data demonstrate for the first time that antioxidants modify the biological activity of dental metals.
Expansion–contraction of photoresponsive artificial muscle regulated by host–guest interactions (2012)

The development of stimulus-responsive polymeric materials is of great importance, especially for the development of remotely manipulated materials not in direct contact with an actuator. Here we design a photoresponsive supramolecular actuator by integrating host-guest interactions and photoswitching ability in a hydrogel. A photoresponsive supramolecular hydrogel with α-cyclodextrin as a host molecule and an azobenzene derivative as a photoresponsive guest molecule exhibits reversible macroscopic deformations in both size and shape when irradiated by ultraviolet light at 365 nm or visible light at 430 nm. The deformation of the supramolecular hydrogel depends on the incident direction. The selectivity of the incident direction allows plate-shaped hydrogels to bend in water. Irradiating with visible light immediately restores the deformed hydrogel. A light-driven supramolecular actuator with α-cyclodextrin and azobenzene stems from the formation and dissociation of an inclusion complex by ultraviolet or visible light irradiation.
Engineering the Glucansucrase GTFR Enzyme Reaction and Glycosidic Bond Specificity: Toward Tailor-Made Polymer and Oligosaccharide Products (2008)

Two long-standing questions about glucansucrases (EC 2.4.1.5) are how they control oligosaccharide versus polysaccharide synthesis and how they direct their glycosidic linkage specificity. This information is required for the production of tailor-made saccharides. Mutagenesis promises to be an effective tool for enzyme engineering approaches for altering the regioselectivity and acceptor substrate specificity. Therefore, we chose the most conserved motif around the transition state stabilizer in glucansucrases for a random mutagenesis of the glucansucrase GTFR of Streptococcus oralis, yielding different variants with altered reaction specificity. Modifications at position S628 achieved by saturation mutagenesis guided the reaction toward the synthesis of short chain oligosaccharides with a drastically increased yield of isomaltose (47%) or leucrose (64%). Alternatively, GTFR variant R624G/V630I/D717A exhibited a drastic switch in regioselectivity from a dextran type with mainly alpha-1,6-glucosidic linkages to a mutan type polymer with predominantly alpha-1,3-glucosidic linkages. Targeted modifications demonstrated that both mutations near the transition state stabilizer, R624G and V630I, are contributing to this alteration. It is thus shown that mutagenesis can guide the transglycosylation reaction of glucansucrase enzymes toward the synthesis of (a) various short chain oligosaccharides or (b) novel polymers with completely altered linkages, without compromising their high transglycosylation activity and efficiency.
The heart and the gut (2013)

The heart and the gut seem to be two organs that do not have much in common. However, there is an obvious and clinically relevant impact of gut functions on the absorption of drugs and oral therapies on the one hand. On the other hand, the gut determines the quantity of nutrient uptake and plays a central role in metabolic diseases. Patients with inflammatory bowel diseases appear to have a higher risk for coronary heart disease despite a lower prevalence of 'classical' risk factors, indicating additional links between the gut and the heart. However, they certainly have a 'leaky' intestinal barrier associated with increased permeability for bacterial wall products. An impaired intestinal barrier function will be followed by bacterial translocation and presence of bacterial products in the circulation, which can contribute to atherosclerosis and chronic heart failure (CHF) as recent data indicate. Impaired cardiac function in CHF vice versa impacts intestinal microcirculation leading to a barrier defect of the intestinal mucosa and increased bacterial translocation. These pathways and the most recent insights into the impact of the gut on acute and chronic heart disease will be discussed in this review.
A phase-I clinical study of autologous tumor cells plus interleukin-2-gene-transfected allogeneic fibroblasts as a vaccine in patients with cancer (1997)

Tumor cells transfected to express immunostimulatory cytokines, or admixed with similarly modified bystander cells, are able to induce immune responses against unmodified tumor cells in animal models. For treatment of human patients, a vaccine composed of autologous tumor cells and IL-2-secreting allogeneic fibroblasts was developed. Autologous tumor cells were isolated from biopsy specimens. A clone (KMST 6.14) of an immortalized human fibroblast line that stably secreted 5290 IU IL-2 per 10(6) cells and per 24 hr was obtained by cationic lipofection with an expression construct for human IL-2 and Neo(r). Fifteen patients with refractory malignant tumors received 3-4 injections of irradiated KMST6.14 and autologous tumor cells in a phase-I clinical trial. Increasing transient inflammatory responses without systemic toxicity developed at vaccination sites and after injections with irradiated tumor cells only (p < 0.05). These sites contained a dense infiltrate of CD3+ T cells with numbers of CD4+ helper cells exceeding those of CD8+ cytotoxic T cells (CTL). CD8+ T-cell lines isolated from vaccination sites of 2 malignant melanoma patients but not of renal-cell carcinoma patients exhibited a dominant lytic activity against autologous tumor cells in vitro. CD8+ T-cell clones established from the vaccination site of 1 of 2 renal-cell carcinoma patients preferentially lysed autologous and partially matched allogeneic renal-cell carcinoma cells. In conclusion, a vaccine composed of IL-2 gene-transfected allogeneic fibroblasts and autologous tumor cells is able to enhance specific anti-tumor T-cell responses in vivo without major side-effects. Malignant melanoma and renal-cell carcinoma appear to be promising entities for testing of similar approaches in future therapeutic trials.
An Experimental Model to Study the in Vivo Survival of von Willebrand Factor (2004)

To explore the molecular basis of von Willebrand factor (VWF) clearance, an experimental model employing VWF-deficient mice was developed. Biodistribution was examined by the injection of radiolabeled VWF, which was primarily directed to the liver with minor amounts in other organs. Disappearance of VWF from plasma was characterized by a rapid initial phase (t((1/2))alpha = 13 min) and a slow secondary phase (t((1/2))beta = 3 h), with a mean residence time (MRT) of 2.8 h. A similar clearance was observed for VWF consisting of only high or low molecular weight multimers, indicating that, in our experimental model, clearance is independent of multimeric distribution. This allowed us to compare the survival of full-length VWF to truncated variants. Deletion of both the amino-terminal D'-D3 and carboxyl-terminal D4-CK domains resulted in a fragment with a similar clearance to wild-type VWF. Deletion of only the D'-D3 region was associated with an almost 2-fold lower recovery and increased clearance (MRT = 1.6 h), whereas deletion of only the D4-CK region resulted in a significantly reduced clearance (MRT = 4.5 h, p < 0.02). These results point to a role of the D'-D3 region in preventing clearance of VWF. Furthermore, replacement of D3 domain residue Arg-1205 by His resulted in a markedly increased clearance (MRT = 0.3 h; p = 0.004). Therefore, this mutation seems to abrogate the protective effect of the D'-D3 region. In vitro analysis of this mutant also revealed a 2-fold reduced affinity for VWF propeptide at low pH, showing that mutation of Arg-1205 results not only in an increased clearance rate but is also associated with an impaired pH-dependent interaction with VWF propeptide.
A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries (2018)

Although the current murine model of bone metastasis using intracardiac (IC) injection successfully recapitulates the process of bone metastasis, further progress in the study of bone metastasis requires a new model to circumvent some limitations of this model. Here, we present a new murine model of bone metastasis achieved by injecting cancer cells through the intra-caudal arterial (CA). This model does not require high technical proficiency, predominantly delivers cancer cells to bone marrow of hind limbs with much higher efficiency than IC injection, and greatly shortens the period of overt bone metastasis development. Moreover, CA injection barely causes acute death of mice, enabling us to inject a larger number of cancer cells to further accelerate the development of bone metastasis with a wide variety of cell lines. Our model may open a new avenue for understanding the bone metastatic processes and development of drugs preventing bone metastasis and recurrence.
[Improvement of quality of life (QOL) and life prolongation by CPT-11 + adriamycin (ADM) therapy: report of 4 cases of non-Hodgkin's lymphoma refractory to conventional chemotherapies]. (1999)

CPT-11 + ADM therapy (CPT-11 40 mg/body x 2 days; Day 1 & 2, combined with ADM 20 to 60 mg/body x 1 day; Day 3) was given to four patients with relapsed and advanced non-Hodgkin's lymphoma, which was refractory to conventional chemotherapies. The symptoms of the patients at the beginning of CPT-11 + ADM therapy were fever (in two cases), dyspnea due to pleural effusion (in two), severe backache (in one), and jaundice with splenomegaly (in one). Their Karnofsky performance scales were 20 or 30%. Soon after the initiation of CPT-11 + ADM therapy, their clinical conditions improved dramatically, and they obtained a partial remission lasting 3.5 to 9 months. During the period of controlling lymphomas by this therapy, all patients had some time at home for 2 to 8 months. The adverse effects were vomiting, diarrhea, neutropenia and thrombocytopenia, but no lethal infection or hemorrhage was seen. We conclude that CPT-11 + ADM therapy is very useful for improvement of QOL and life prolongation of patients with non-Hodgkin's lymphoma, which is refractory to conventional chemotherapies and is even disseminated.
Evidence That the Transition of HIV-1 Gp41 into a Six-Helix Bundle, Not the Bundle Configuration, Induces Membrane Fusion (2000)

Many viral fusion proteins exhibit a six-helix bundle as a core structure. HIV Env-induced fusion was studied to resolve whether membrane merger was due to the transition into the bundle configuration or occurred after bundle formation. Suboptimal temperature was used to arrest fusion at an intermediate stage. When bundle formation was prevented by adding inhibitory peptides at this stage, membranes did not merge upon raising temperature. Inversely, when membrane merger was prevented by incorporating lysophosphatidylcholine (LPC) into cell membranes at the intermediate, the bundle did not form upon optimizing temperature. In the absence of LPC, the six-helix bundle did not form when the temperature of the intermediate was raised for times too short to promote fusion. Kinetic measures showed that after the temperature pulse, cells had not advanced further toward fusion. The latter results indicate that bundle formation is the rate-limiting step between the arrested intermediate and fusion. Electrical measures showed that the HIV Env-induced pore is initially large and grows rapidly. It is proposed that bundle formation and fusion are each contingent on the other and that movement of Env during its transition into the six-helix bundle directly induces the lipid rearrangements of membrane fusion. Because peptide inhibition showed that, at the intermediate stage, the heptad repeats of gp41 have become stably exposed, creation of the intermediate could be of importance in drug and/or vaccine development.
Inhibition of In Vitro Splicing of a Group I Intron of Pneumocystis carinii (1994)

Unlike its mammalian hosts, the opportunistic fungal pathogen Pneumocystis carinii harbors group I self-splicing introns in its chromosomal genes encoding rRNA. This difference between pathogen and host suggests that intron splicing is a promising target for chemotherapy. We have found that intron splicing in vitro is inhibited by the anti-Pneumocystis agent pentamidine and by a series of pentamidine analogues, as well as by some aminoglycosides, tetracycline, L-arginine and ethidium bromide. Further studies will be needed to determine if this is the mechanism of action of pentamidine against P. carinii.
Optimal Scheduling of Multicluster Tools With Constant Robot Moving Times, Part I: Two-Cluster Analysis (2010)

In semiconductor manufacturing, finding an efficient way for scheduling a multicluster tool is critical for productivity improvement and cost reduction. This two-part paper analyzes optimal scheduling of multicluster tools equipped with single-blade robots and constant robot moving times. In this first part of the paper, a resource-based method is proposed to analytically derive closed-form expressions for the minimal cycle time of two-cluster tools. We prove that the optimal robot scheduling of two-cluster tools can be solved in polynomial time. We also provide an algorithm to find the optimal schedule. Examples are presented to illustrate the proposed approaches and formulations.
Quantifying the cost of context switch (2007)

Measuring the indirect cost of context switch is a challenging problem. In this paper, we show our results of experimentally quantifying the indirect cost of context switch using a synthetic workload. Specifically, we measure the impact of program data size and access stride on context switch cost. We also demonstrate the potential impact of OS background interrupt handling on the measurement accuracy. Such impact can be alleviated by using a multi-processor system on which one processor is employed for context switch measurement while the other runs OS background tasks.
Organometallic Reactivity on a Calix[4]arene Oxo Surface. Synthesis and Rearrangement of Zr−C Functionalities Anchored to a Calix[4]arene Moiety (1997)

This report concerns the formation and the main properties of Zr−C functionalities supported by the O4 matrix of either the monoalkylated (trianionic) or dialkylated (dianionic) forms of [p-But-calix[4]arene] (1). The synthesis of the starting materials [p-But-calix[4]-(OMe)2(O)2ZrCl2] (4) and [{μ-p-But-calix[4]-(OMe)(O)3}2 Zr2Cl2] (10) has been performed via the lithiation of the corresponding protic forms, [p-But-calix[4]-(OMe)2(OH)2] (2) and [p-But-calix[4]-(OMe)(OH)3] (8), followed by reaction with ZrCl4·(thf)2. Complex 4 undergoes a facile base-induced (base = Et3N, Py) demethylation, leading to the monomethoxy derivative [p-But-calix[4]-(OMe)(O)3ZrCl2]-[MeNEt3]+ (5) and ionization of the Zr−Cl bond to give [p-But-calix[4]-(OMe)2(O)2Zr(OTf)2] (6). The alkylation of 4 led to the corresponding dialkylaryl derivatives [p-But-calix[4]-(OMe)2(O)2ZrR2] (R = Me, 12; R = CH2Ph, 13; R = CH2SiMe3, 14; R = p-MeC6H4, 15]. They undergo a base-induced demethylation and dealkylation illustrated by the obtention of [p-But-calix[4]-(OMe)(O)3Zr(CH2Ph)(Py)] (18), while the thermal decomposition gave a particularly interesting result in the case of 15, with the formation of the corresponding η2-benzyne, [p-But-calix[4]-(OMe)2(O)2Zr(η2-MeC6H3)] (16). Cationic alkyl derivatives of zirconium have been obtained, in the case of 13, using the monoelectronic oxidizing agent [Cp2Fe]+ or a strong Lewis acid such as [B(C6F5)3], [p-But-calix[4]-(OMe)2(O)2Zr(CH2Ph)]+BPh4- (19); [p-But-calix[4]-(OMe)2(O)2Zr(CH2Ph)(thf)]+BPh4- (20); and [p-But-calix[4]-(OMe)2(O)2Zr(CH2Ph)]+ [B(C6F5)3(CH2Ph)]- (21). The cationic alkyl derivatives undergo easy demethylation by pyridine to give 18. The alkylation of 10 with LiPh led to a dimeric dimetallic aryl compound, [{μ-p-But-calix[4]-(OMe)(O)3}2Zr2Ph2] (22), where the calix[4]arene unit bridges two metal atoms and the methoxy groups are only weakly bound to the metal. The spectator methoxy group binds strongly to the metal in the monomeric η2-iminoacyl [p-But-calix[4]-(OMe)(O)3Zr(ButNCPh)] (23), formed from the migratory insertion of ButNC into the Zr−Ph in 22. The proposed structures have been supported by X-ray analyses carried out on 4, 6, 13, 16, 22, and 23.
Effect of injected bovine interferon-αI1 on oestrous cycle length and pregnancy success in sheep (1991)

In Exp. 1 twice daily i.m. injections of 2 mg recombinant bovine IFN-alpha I1 (rboIFN-alpha I1) (N = 24) or placebo (N = 25) were administered to ewes from Day 12 to Day 16 during a normal oestrous cycle. Treatment did not increase (P greater than 0.10) oestrous cycle length (20.7 +/- 1.2 versus 18.5 +/- 1.4 days). In Exp. 2, ewes were injected twice daily with 2 mg IFN (N = 34) or placebo (N = 36) from Days 11 to 18 after natural mating. The rboIFN-alpha I1 significantly (P = 0.05) improved pregnancy rate (79% versus 58%) as determined by a failure of ewes to return to oestrus within 50 days. The number of ewes that lambed was greatest in the rboIFN-alpha I1-treatment group (71% versus 50%; P = 0.07), and no teratogenic effects were observed in the young born to IFN-treated ewes. The study was repeated a second year with a more fecund group of ewes (Exp. 3). More (P = 0.08) ewes injected with rboIFN-alpha I1 (58/65) than placebo-treated ewes (48/61) were judged pregnant by ultrasound. Again more ewes lambed (55 versus 45) and more lambs were born (98 versus 80) from the rboIFN-alpha I1-treated group. Combining the data from both studies revealed a significant (P = 0.01) effect of treatment. The amount of antiviral activity in jugular vein blood of ewes injected with rboIFN-alpha I1 (2 mg) was determined over time in Exp. 4. Activity rose to a maximum (approximately 450 IRU/ml) within 1-2 h and declined by over 75% in 24 h. Single injections of 1, 2 and 5 mg in buffer or 2 mg emulsified in sesame oil all gave similar profiles of antiviral activity in jugular blood over a 48-h period. In Exp. 5, antiviral activity was measured in uterine vein, ovarian artery and jugular vein serum of untreated pregnant (N = 7) and non-pregnant (N = 11) ewes at Day 15 after mating. Activity was detected in the uterine vein (58 +/- 19 IRU/ml) of all pregnant ewes. The observations in Exps 1-5 are consistent with a role for conceptus-derived IFN-alpha in maternal recognition of pregnancy and suggest that supplemental IFN-alpha might be useful in improving pregnancy success in sheep.