gebhart/patrepeval huggingface dataset:
Effects of cabergoline on reproduction in three families of Australian marsupials (1998)

The effects of the prolactin inhibiting drug, cabergoline, on pregnant and lactating marsupials were investigated in four species from three diverse families: the tammar wallaby, Macropus eugenii, the quokka, Setonix brachyurus, the brushtail possum, Trichosurus vulpecula, and the fat-tailed dunnart, Sminthopsis crassicaudata. In tammar wallabies, 20 micrograms cabergoline kg-1 injected intramuscularly 1 day before expected birth did not alter the timing of parturition but neonates died within a day of birth, suggesting that the onset of lactation was compromised. During early lactation in tammars (56-69 days post partum), an intramuscular injection transiently retarded growth of the young, although they subsequently survived. This treatment induced reactivation of the quiescent corpus luteum and the blastocyst from diapause, so a new birth occurred 26-27 days later, despite the continued sucking of the young in the pouch. Intramuscular injection during late lactation (166-199 days post partum) apparently suppressed milk secretion since pouch young lost up to 20% of their bodyweight or died within 7 days of treatment. Oral administration of cabergoline had no effect on the growth of the young or on the quiescent corpus luteum and diapausing blastocyst. Quokkas showed similar responses to tammars after treatment in late lactation. Possums and dunnarts were less sensitive to injected cabergoline than the two macropodid species, and possums showed no response to oral administration. The lack of response of these marsupial species to oral cabergoline treatment suggests that accidental ingestion of baits, containing 20 micrograms cabergoline kg-1, used to control introduced eutherian pests such as the red fox, Vulpes vulpes, or the feral cat, Felis cattus, should not affect the reproduction of native marsupials.
Tug-of-War in Motor Protein Ensembles Revealed with a Programmable DNA Origami Scaffold (2012)

Cytoplasmic dynein and kinesin-1 are microtubule-based motors with opposite polarity that transport a wide variety of cargo in eukaryotic cells. Many cellular cargos demonstrate bidirectional movement due to the presence of ensembles of dynein and kinesin, but are ultimately sorted with spatial and temporal precision. To investigate the mechanisms that coordinate motor ensemble behavior, we built a programmable synthetic cargo using three-dimensional DNA origami to which varying numbers of DNA oligonucleotide-linked motors could be attached, allowing for control of motor type, number, spacing, and orientation in vitro. In ensembles of one to seven identical-polarity motors, motor number had minimal affect on directional velocity, whereas ensembles of opposite-polarity motors engaged in a tug-of-war resolvable by disengaging one motor species.
Isolated Light Chain of Tetanus Toxin Inhibits Exocytosis: Studies in Digitonin‐Permeabilized Cells (1989)

Previous work indicates that the heavy chain of tetanus toxin is responsible for the binding of the toxin to the neuronal membrane and its subsequent internalization. In the present study, the light chain of tetanus toxin mimicked the holotoxin in inhibiting Ca2+-dependent secretion of [3H]norepinephrine from digitonin-permeabilized adrenal chromaffin cells. Preincubation of tetanus toxin with monoclonal antibodies to the light chain prevented the inhibition by tetanus toxin. Preincubation of tetanus toxin with nonimmune ascites fluid or with monoclonal antibodies directed against the C fragment (the C-terminal of the heavy chain) or the heavy-chain portion of the B fragment did not prevent inhibition by tetanus toxin. The data indicate that the light chain is responsible for the intracellular blockade of exocytosis.
Towards purification of adenoviral vectors based on membrane technology (2008)

Given increasing applications of recombinant adenoviruses for gene therapy and vaccination, there is a need for highly robust and fast purification platforms for their large scale manufacture. Traditional chromatographic methods using resins as matrices have several limitations such as high-pressure drops and slow processing rates due to pore diffusion and channelling of the feed through the bed. In contrast, membrane adsorbers offer the advantage of fast, gentle, and effective isolation. Furthermore, membranes are easy to use, no column packing is needed and, when used as disposables, no cleaning validation is necessary, representing a substantial advantage to meet cGMP requirements. In this work, a strategy for purification of adenovirus vectors from cell-culture bulks fully based on membrane devices is presented. Ultrafiltration membranes with molecular weight cutoffs of 300, 500, and 750 kDa were tested for the concentration of cell-culture supernatant after an initial clarification step. The results show that the use of ultrafiltration/diafiltration membranes not only concentrates the virus but also leads to the removal of 90% of host cell DNA and proteins in the retentate. Two membrane adsorbers (Sartobind Q and Sartobind anion direct) were evaluated for adenovirus vectors capture and purification. To define the best operating conditions, the effect of pH, conductivity, and recirculation of load bulk on the recovery yield of infectious adenoviruses were evaluated. Sartobind anion direct allows for higher recovery yields (up to 62%) of infectious adenoviruses than Sartobind Q; identical ratios between total and infectious adenoviruses (TP/IP) were achieved for both membrane adsorbers. The overall recovery yield of the process is approximately 52%; this work credits membrane technology as an alternative for the concentration and purification of adenoviruses and as a promising solution for downstream processing of other viral vectors.
Structure—Property Relationship of Permutite‐Like Amorphous Silicates, Nax+2yM3+xSi1‐xO2+y (M3+: Al, Mn, Fe, Y), for Ion‐Exchange Reactions. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Real-time diagnostic imaging with a novel x-ray detector with multiple screen-CCD sensors (1998)

In reference 1 we have presented the principle of an X-ray detector based upon a screen coupled to an array of multiple CCD sensors. In reference 2 we focus on the characterization of the image quality: resolution (MTF) and noise behavior in the overlap area. Simple (and cheap) low F# lenses likely show distortion which means that not all imaged pixels have the same magnification. This may affect resolution. Lenses with (some) barrel distortion have the benefit of less vignetting. The correction of distortion in combination with a rotation adjustment requires interpolation. Interpolation affects the noise properties so care must be taken in order to avoid that the noise characterization of the reconstructed image mosaic i.e. the noise texture becomes spatially non uniform. We present an analysis of the influence of lens distortion and interpolation in cases of small rotation correction on the image mosaic. The image processing appears not to diminish the image quality provided the processing parameters are set correctly. The calibration of the imaging mosaic geometry is crucial. We therefore present a robust extraction algorithm. In this paper our main interest is on MTF and quantum noise properties. The lab prototype hardware is designed such (cubic spline interpolation) that also the lens distortion can be compensated. For this purpose ASICs are designed by the company AEMICS. This enables relative cheap optical components with low F# and a short building length. We have obtained and will present radiographic exposures of static phantoms.
A Splice Variant of β-Secretase Deficient in the Amyloidogenic Processing of the Amyloid Precursor Protein (2001)

beta-Secretase (BACE) initiates the amyloidogenic processing of the amyloid precursor protein leading to the generation of the beta-amyloid, the main component of Alzheimer's disease senile plaques. BACE is a type I transmembrane aspartyl protease of 501 amino acids. Here we describe a novel BACE mRNA lacking 132 base pairs that is expressed in the pancreas but not in the brain. Sequence alignment indicates that the deleted fragment matches the terminal two-thirds of exon 3. The new BACE variant is short of a 44-amino acid region located between the two catalytic aspartyl residues. Accordingly, a 50-kDa form of BACE (BACE457) is detected in the human pancreas. When expressed in cells, BACE457 colocalizes with the marker for the endoplasmic reticulum BiP. Moreover, BACE457 remains in a proenzymatic and endoglycosidase H-sensitive state, suggesting that its transport along the secretory pathway is blocked at the level of the endoplasmic reticulum. Notably, this novel form of BACE does not contribute to the processing of the amyloid precursor protein. Our findings suggest that tissue-specific splicing of the BACE mRNA may explain the observation that in the human pancreas robust transcription of the BACE gene does not translate into recovered enzymatic activity.
<title>Fabrication and imaging of quantum-well wire structures</title> (1992)

Quantum well wire structures in metalorganic vapor phase epitaxy (MOVPE) grown Ga<SUB>.53</SUB>In<SUB>.47</SUB>As/InP and in Ga<SUB>.85</SUB>In<SUB>.15</SUB>As/GaAs have been fabricated by electron beam lithography and subsequent metalorganic reactive ion etching (MORIE) and/or wet etching. The dry etching was optimized for low-damage conditions and for mask-to-wafer pattern transfer. In the wet etching process, an underetching was implemented in order to reduce the linewidth defined by the etching mask. A wet etching step has been used after the dry etching for removal of the partly damaged surface region and for smoothing of the sidewalls of the wires. Differently processed areas were excited selectively by low- temperature cathodoluminescence (CL) from which the optical quality of the wire material was evaluated and blue shifts for the wires as large as 10 meV were observed. Individual wires have also been imaged and effects of one-dimensional exciton diffusion have been probed.
Stabilization of hepatitis C virus RNA by an Ago2–miR-122 complex (2012)

MicroRNAs (miRNAs) are small noncoding RNAs that regulate eukaryotic gene expression by binding to regions of imperfect complementarity in mRNAs, typically in the 3' UTR, recruiting an Argonaute (Ago) protein complex that usually results in translational repression or destabilization of the target RNA. The translation and decay of mRNAs are closely linked, competing processes, and whether the miRNA-induced silencing complex (RISC) acts primarily to reduce translation or stability of the mRNA remains controversial. miR-122 is an abundant, liver-specific miRNA that is an unusual host factor for hepatitis C virus (HCV), an important cause of liver disease in humans. Prior studies show that it binds the 5' UTR of the messenger-sense HCV RNA genome, stimulating translation and promoting genome replication by an unknown mechanism. Here we show that miR-122 binds HCV RNA in association with Ago2 and that this slows decay of the viral genome in infected cells. The stabilizing action of miR-122 does not require the viral RNA to be translationally active nor engaged in replication, and can be functionally substituted by a nonmethylated 5' cap. Our data demonstrate that a RISC-like complex mediates the stability of HCV RNA and suggest that Ago2 and miR-122 act coordinately to protect the viral genome from 5' exonuclease activity of the host mRNA decay machinery. miR-122 thus acts in an unconventional fashion to stabilize HCV RNA and slow its decay, expanding the repertoire of mechanisms by which miRNAs modulate gene expression.
Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast cancer risk. (1998)

Metabolism of estradiol occurs via two mutually exclusive hydroxylative pathways, yielding metabolites of divergent biological properties. 2-hydroxyestrone (2OHE1) is anti-estrogenic while 16 alpha-hydroxyestrone (16 alpha OHE1) is a potent estrogen. The ratio of 2OHE1 to 16 alpha OHE1 (2/16 alpha-OHE1 ratio) represents the net in vivo estrogenic activity. In this study, we sought to determine if the urinary 2/16 alpha-OHE1 ratio could be a predictor of breast cancer risk and the factors which influence this ratio. Variables analysed included age at diagnosis, menopausal status, parity, use of oral contraceptives, body mass index, serum levels of insulin-like growth factor-I (IGF-I), IGF binding proteins (BPs) and the presence of breast cancer. Serum and urine were collected from 65 breast cancer patients and 36 controls after an overnight fast. Urinary estrogen metabolites were measured by enzyme immunoassays while serum levels of IGF-I, BP-1 and BP-3 were determined by immunoradiometric assays. 2OHE1 levels and 2/16 alpha-OHE1 ratios were significantly lower (P < 0.05) while 16 alpha OHE1 levels were higher (P < 0.01) in cancer patients. Multiple linear regression analysis showed that levels of urinary metabolites were influenced by parity and breast carcinoma. 2/16 alpha-OHE1 ratio correlated positively with serum BP-3 level (P = 0.03). By multiple logistic regression, 2/16 alpha-OHE1 ratio was the most significant factor predictive of breast cancer. The odds ratio for women with higher 2/16 alpha-OHE1 ratios was 0.10 (0.03-0.38, 95% confidence interval). In conclusion, the profile of urinary estradiol metabolites was distinctly altered in breast cancer patients. In addition, BP-3 may be a potential mechanism by which estradiol metabolites influence breast cancer progression. As 16 alpha OHE1 has been shown to initiate neoplastic transformation of mammary epithelial cells, the 2/16 alpha-OHE1 ratio may serve as a biomarker of increased risk of breast cancer.
Managing Premedications and the Risk for Reactions to Infusional Monoclonal Antibody Therapy (2008)

Monoclonal antibodies-including rituximab, alemtuzumab, trastuzumab, bevacizumab, cetuximab, and panitumumab-have improved the treatment of various malignancies. Although generally better tolerated with less toxicity than conventional anticancer agents, monoclonal antibodies may cause infusion-related reactions like other infusional agents. The incidence of infusion reactions varies by agent, but severe events occur only occasionally, mostly with the first or second infusion. Although the exact etiology of infusion reactions remains unclear, they may arise via either IgE- or non-IgE-dependent mechanisms. There is a compelling clinical need to improve the risk assessment for severe infusion reactions. The recent identification of pre-existing IgE crossreacting with cetuximab, its association with severe reactions, and regional variation in the prevalence may provide a marker for high-risk assessment. Premedication with antihistamines, acetaminophen, and/or corticosteroids is a common practice to prevent infusion reactions with all monoclonal antibodies. However, a recent observational study suggests that premedication may no longer be necessary after the second infusion of cetuximab if patients did not develop any symptoms with the first two infusions. Considering the heterogeneity of infusion reactions, clinicians need to recognize the underlying nature of these events in order to identify patients at risk as well as provide optimal prophylactic measures and management of symptoms.
Heparin/heparan sulphate binding in the TGF-β cytokine superfamily (2006)

The TGF-beta (transforming growth factor-beta) cytokine superfamily in mammals contains some 30 members. These dimeric proteins are characterized by a strongly conserved cystine knot-based structure. They regulate the proliferation, differentiation and migration of many cell types, and therefore have important roles in morphogenesis, organogenesis, tissue maintenance and wound healing. Thus far, around one-quarter of these cytokines have been shown to bind to heparin and heparan sulphate. Well-established examples are the TGF-beta isoforms 1 and 2, and the BMPs (bone morphogenetic proteins) -2 and -4. In studies in my laboratory, we have shown that GDNF (glial-cell-line-derived neurotrophic factor) and its close relatives neurturin and artemin bind to heparin and heparan sulphate with high affinity. We have reported previously that binding of GDNF is highly dependent on the presence of 2-O-sulphate groups. More recently, we and others have been investigating the heparin/heparan sulphate-binding properties of BMP-7, which is a representative of a distinct BMP subgroup from that of BMPs -2 and -4. Interestingly, several of the various specific BMP antagonist proteins also bind to heparin and heparan sulphate. Much remains to be learnt about the nature and role of glycosaminoglycan interactions in the TGF-beta superfamily, but current work suggests that these cytokines do not share a single highly conserved heparin/heparan sulphate-binding site.
Very high mobility two-dimensional hole gas in Si/GexSi1−x/Ge structures grown by molecular beam epitaxy (1993)

Modulation-doped Si/GexSi1−x/Ge/GexSi1−x structures were fabricated in which a thin Ge layer was employed as the conduction channel for the two-dimensional hole gas. The strained heterostructure was fabricated on top of a low threading dislocation density, totally relaxed, GexSi1−x buffer layer with a linearly graded Ge concentration profile. The best mobility of the two-dimensional hole gas is 55 000 cm2/V s at 4.2 K with a concentration-dependent hole effective mass of ≤0.10m0. The effect of the Ge/GeSi interface roughness on the 2DHG mobility was studied.
沉积岩数据库:计算机的应用(英文) (1995)

岩石学数据在许多地质统计分析中是相当有用的。为了得出焦伊布尔哈德地区的焦因蒂亚布尔区和锡尔赫特地区焦伊布尔哈德灰岩区的构造、地层和沉积作用情况,已作了大量的详细的野外工作和室内分析。已对锡尔赫特地区和焦伊布尔哈德地区的灰岩作了化学分析,且对 Tipam 砂岩作了矿物分析。所获取数据可应用于 SEDBA。用于 SEDBA 的参数必须是精确的和沉积成因的。
The dangers of replication and a solution (1996)

Update anywhere-anytime-anyway transactional replication has unstable behavior as the workload scales up: a ten-fold increase in nodes and traffic gives a thousand fold increase in deadlocks or reconciliations. Master copy replication (primary copy) schemes reduce this problem. A simple analytic model demonstrates these results. A new two-tier replication algorithm is proposed that allows mobile (disconnected) applications to propose tentative update transactions that are later applied to a master copy. Commutative update transactions avoid the instability of other replication schemes.
Understanding the fluid dynamics associated with macro scale ultrasonic separators (2015)

Acoustic standing wave fields are widely used in MEMS applications to separate micron sized particles from fluids. However, the use and understanding of macro scale ultrasonic separators are still limited and challenging. New macro-scale, ultrasonic separators are presented that use multidimensional standing waves to trap and generate tightly packed clusters of suspended particles which continuously grow and drop out of a flowing fluid mixture. Typical flow Reynolds numbers are less than 50, particle concentrations up to 20% and ultrasonic standing wave fields at frequencies of 1-3 MHz and acoustic pressure amplitudes of about 1 MPa. At such small Reynolds numbers the flow is dominated by shear forces and the drag on clumps of particles is significantly lower than Stokes' drag on a single particle. The fluid dynamics associated with these systems is extremely complex due to the coupling between the fluid flow field, suspended particles, and acoustic radiation forces. This work discusses the key physics involved and explains our current understanding of operation of macro scale acoustic separators. The status of CFD (Computational Fluid Dynamics) efforts to predict the flow fields and particle clustering in such systems is presented and compared to experimental results.
Some problems of mutagenesis induced by base analogues. (1984)

A brief survey is presented on the problem of base-analogue-induced mutagenesis. The main conclusions are as follows: (i) Since some of the base analogues may induce the SOS response, the probability exists that, in these cases, some of the mutants may arise via umuC-mediated misrepair mutagenesis; (ii) At least two cellular systems may influence base-analogue-induced mutagenesis: DNA polymerases and mismatch repair systems. Whereas the first may influence the yield of mutations, the second may affect both the yield and specificity of mutations; (iii) Specificity of base-analogue-induced mutations is much more differentiated than hitherto believed. Some of the base analogues are highly specific mutagens, e.g. N4- hydroxycytidine , which induces almost exclusively AT----GC base-pair transitions, whereas the others, e.g. 2-aminopurine and 2-amino-N6- methoxyadenine , may induce both transitions and transversions.
Mutasynthesis of Enterocin and Wailupemycin Analogues (2003)

Inactivation of the novel phenylalanine ammonia lyase gene encP, whose product is a key component in the biosynthetic pathway to benzoyl-coenzyme A (CoA) in the bacterium Streptomyces maritimus, resulted in the loss of production of the benzoate-primed polyketides enterocin and wailupemycin G. A series of cinnamate and benzoate derivatives were administered to the DeltaencP mutant, resulting in the formation of novel analogues bearing p-fluorobenzoate, 2- and 3-thiophenecarboxylate, and cyclohex-1-enecarboxylate residues. Given that the benzoate:CoA ligase EncN was evaluated to have broad in vitro substrate specificity towards aryl acids, the strict starter unit specificity observed in vivo indicates that the enterocin type II polyketide synthase (PKS) exerts selective control over the choice of starter units. This study represents the first mutasynthesis experiments with iterative type II PKSs.
Formulation of a Medical Food Cocktail for Alzheimer's Disease: Beneficial Effects on Cognition and Neuropathology in a Mouse Model of the Disease (2010)

In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD.
Influenza Promotes Collagen Deposition via αvβ6 Integrin-mediated Transforming Growth Factor β Activation (2014)

Influenza infection exacerbates chronic pulmonary diseases, including idiopathic pulmonary fibrosis. A central pathway in the pathogenesis of idiopathic pulmonary fibrosis is epithelial injury leading to activation of transforming growth factor β (TGFβ). The mechanism and functional consequences of influenza-induced activation of epithelial TGFβ are unclear. Influenza stimulates toll-like receptor 3 (TLR3), which can increase RhoA activity, a key event prior to activation of TGFβ by the αvβ6 integrin. We hypothesized that influenza would stimulate TLR3 leading to activation of latent TGFβ via αvβ6 integrin in epithelial cells. Using H1152 (IC50 6.1 μm) to inhibit Rho kinase and 6.3G9 to inhibit αvβ6 integrins, we demonstrate their involvement in influenza (A/PR/8/34 H1N1) and poly(I:C)-induced TGFβ activation. We confirm the involvement of TLR3 in this process using chloroquine (IC50 11.9 μm) and a dominant negative TLR3 construct (pZERO-hTLR3). Examination of lungs from influenza-infected mice revealed augmented levels of collagen deposition, phosphorylated Smad2/3, αvβ6 integrin, and apoptotic cells. Finally, we demonstrate that αvβ6 integrin-mediated TGFβ activity following influenza infection promotes epithelial cell death in vitro and enhanced collagen deposition in vivo and that this response is diminished in Smad3 knock-out mice. These data show that H1N1 and poly(I:C) can induce αvβ6 integrin-dependent TGFβ activity in epithelial cells via stimulation of TLR3 and suggest a novel mechanism by which influenza infection may promote collagen deposition in fibrotic lung disease.