gebhart/patrepeval huggingface dataset:
Cystatin C Antagonizes Transforming Growth Factor β Signaling in Normal and Cancer Cells (2004)

Abstract Cystatin C (CystC) is a secreted cysteine protease inhibitor that regulates bone resorption, neutrophil chemotaxis, and tissue inflammation, as well as resistance to bacterial and viral infections. CystC is ubiquitously expressed and present in most bodily fluids where it inhibits the activities of cathepsins, a family of cysteine proteases that can promote cancer cell invasion and metastasis. Transforming growth factor β (TGF-β) is a multifunctional cytokine endowed with both tumor-suppressing and tumor-promoting activities. We show herein that TGF-β treatment up-regulated CystC transcript and protein in murine 3T3-L1 fibroblasts. Moreover, CystC mRNA expression was down-regulated in ∼50% of human malignancies, particularly cancers of the stomach, uterus, colon, and kidney. Overexpression of CystC in human HT1080 fibrosarcoma cells antagonized their invasion through synthetic basement membranes in part via a cathepsin-dependent pathway. Independent of effects on cathepsin activity, CystC also reduced HT1080 cell gene expression stimulated by TGF-β. Invasion of 3T3-L1 cells occurred through both cathepsin- and TGF-β-dependent pathways. Both pathways were blocked by CystC, but only the TGF-β-dependent pathway was blocked by a CystC mutant (i.e., Δ14CystC) that is impaired in its ability to inhibit cathepsin activity. Moreover, CystC and Δ14CystC both inhibited 3T3-L1 cell gene expression stimulated by TGF-β. We further show that CystC antagonized TGF-β binding to its cell surface receptors, doing so by interacting physically with the TGF-β type II receptor and antagonizing its binding of TGF-β. Collectively, our findings have identified CystC as a novel TGF-β receptor antagonist, as well as a novel CystC-mediated feedback loop that inhibits TGF-β signaling.
Identification of neuropeptide Y receptors in cultured astrocytes from neonatal rat brain (1993)

Specific binding sites for neuropeptide Y could be demonstrated in primary cultures of astrocytes from neonatal rat brain. Neuropeptide Y binding was saturable, reversible, and temperature dependent as revealed by saturation studies and kinetic experiments. Scatchard analysis of equilibrium binding data indicated a single population of high-affinity binding sites with respective KD and Bmax values of 0.43 nM and 6.9 fmol/2.7 x 10(5) cells. Physiological responses induced by neuropeptide Y could be detected in a distinct subpopulation of cultured astrocytes on the basis of two criteria: 1) electrophysiological responses and 2) single cell measurements of changes in [Ca2+]i. In that fraction of cells responding (20-70%, varying among cultures from different preparations), brief application of neuropeptide Y led to a membrane potential depolarization, lasting several minutes. When the membrane was clamped close to the resting membrane potential using the whole-cell patch-clamp technique, neuropeptide Y induced an inward current with a similar time course as the neuropeptide Y-induced membrane depolarization. As detected by single cell microfluorimetric (fura-2) measurements neuropeptide Y induced an increase of [Ca2+]i which was caused by the entry of extracellular Ca2+. Both the [Ca2+]i increase and the electrophysiological responses were unaffected by pretreatment of the astrocytes with pertussis toxin.
Tailored drug release profiles from bioerodible polyanhydride microspheres (2003)

The fabrication, morphological characterization, and drug release kinetics from microspheres of three bioerodible polyanhydrides, poly[1,6-bis(p-carboxyphenoxy)hexane] (poly(CPH)), poly(sebacic anhydride) (poly(SA)), and the copolymer poly(CPH-co-SA) 50:50 (CPH:SA 50:50) are reported. Tailored release profiles of a burst followed by zero-order release are obtained by appropriately combining the microspheres in 'cocktails.'.
Selective binding of 2′-F-c-di-GMP to Ct-E88 and Cb-E43, new class I riboswitches from Clostridium tetani and Clostridium botulinum respectively (2013)

C-di-GMP is a second messenger in bacteria and partly regulates bacterial physiology by binding to class I and II riboswitches. Four class I c-di-GMP riboswitch aptamer candidates, Ct-E88, Cb-17B, Cb-E43 and Cd-630 RNAs, selected from a GEMM RNA sequence motif in the Rfam database, were expressed and experimentally verified to bind to c-di-GMP. The two newly characterized c-di-GMP riboswitches, Ct-E88 and Cb-E43, bound c-di-GMP with nanomolar Kd whereas the affinities of Cb-17B and Cd-630 for c-di-GMP were at least a 100-fold weaker. Interestingly, whereas the three riboswitches (Vc2, Et-E88 and Cb-E43) bound c-di-GMP with similar Kd values, 2'-modified analogs of c-di-GMP differentially bound to these three class I aptamers. For example, 2'-F-c-di-GMP bound Vc2 with a Kd value of 102 nM whereas the Kd value of 2'-F-c-di-GMP-Ct-E88 is 43 μM (422× higher than that for Vc2 RNA), revealing that there are differences in the binding sites of functional class I c-di-GMP riboswitches.
1,25-Dihydroxyvitamin D3 represses tropoelastin expression by a posttranscriptional mechanism. (1992)

Tropoelastin expression is down-regulated by exposure to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and we present data indicating that this repression is primarily controlled by a posttranscriptional mechanism. Steady-state and functional levels of tropoelastin mRNA were coordinately repressed by 10(-7) M 1,25 (OH)2D3 in fetal bovine chondrocytes, but transcription, as determined by nuclear runoff assay, was not appreciably influenced in fetal bovine chondrocytes or in rat lung fibroblasts. Similarly, exposure to 1,25(OH)2D3 did not influence chloramphenicol acetyl-transferase activity expressed by a human tropoelastin promoter-expression construct in either cell type. Exposure to cycloheximide had little effect on tropoelastin mRNA levels in control cells but partially restored tropoelastin mRNA levels in cells pretreated with 1,25(OH)2D3 and prevented repression when added together with 1,25(OH)2D3. Similarly, simultaneous exposure to actinomycin D and 1,25(OH)2D3 attenuated the down-regulation of tropoelastin. These data indicate that repression of tropoelastin steady-state mRNA levels by 1,25(OH)2D3 is primarily mediated by a posttranscriptional mechanism that requires both transcription and protein synthesis for full effect.
Human and rodent sequence analogs of Alzheimer's amyloid βA4 share similar properties and can be solubilized in buffers of pH 7.4 (1991)

The filamentous amyloid protein aggregates found in the brain of patients affected with Alzheimer's disease principally consist of a peptide termed beta A4, according to its secondary structure of beta-pleated sheets and its molecular mass of about 4 kDa. It has a length of up to 42 or 43 residues. By chemical means, we have synthesized peptide analogs corresponding to the human and rodent beta A4 sequences. We describe structural and functional properties of peptides spanning residues 1-43, 10-23, 1-27 and 4-27 of beta A4. The peptides have been tested for their ability to form filaments in vitro. Their solubilities and secondary structures in solution and in the solid state have been used to detect differences between the properties of human and rodent beta A4 sequences. We show that mouse and rat beta A4 homologs are as amyloidogenic as the human sequence. The absence of amyloid deposits in the brain of aged rats and mice is therefore not due to the three amino acid substitutions identified within the sequence which is homologous to beta A4 of humans. Moreover, peptides corresponding to residues 1-27 of human and rodent beta A4 are solubilized under physiological conditions; thus they are very unlikely to form stable filaments in vivo.
MEGALOMICIN, A NEW MACROLIDE ANTIBIOTIC COMPLEX PRODUCED BY MICROMONOSPORA (1969)

A new macrolide antibiotic complex has been isolated from fermentation broths of two strains of a news pecies of Micromonospora, M. megalomicea sp. n. The antibiotic complex has been differentiated from other known macrolides and methods for its production, isolation and separation of components have been devised. Like other macrolides, it is primarily active against gram-positive bacteria and is more active at an alkaline pH. Of the four known components, megalomicin A has been studied most extensively. It has activity equal to or slightly less than that of erythromycin both in vitro and in vivo. In dogs dosed orally, it is better tolerated and gives higher peak serum levels with a much greater duration than erythromycin.
Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina (2002)

Retinoids are chromophores involved in vision, transcriptional regulation, and cellular differentiation. Members of the short chain alcohol dehydrogenase/reductase superfamily catalyze the transformation of retinol to retinal. Here, we describe the identification and properties of three enzymes from a novel subfamily of four retinol dehydrogenases (RDH11-14) that display dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols with C(15) pro-R specificity. RDH11-14 could be involved in the first step of all-trans- and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor (RDH12) and retinal pigment epithelial cells (RDH11). The dual-substrate specificity of RDH11 explains the minor phenotype associated with mutations in 11-cis-retinol dehydrogenase (RDH5) causing fundus albipunctatus in humans and engineered mice lacking RDH5. Furthermore, photoreceptor RDH12 could be involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments. These newly identified enzymes add new elements to important retinoid metabolic pathways that have not been explained by previous genetic and biochemical studies.
CMAP: contig mapping and analysis package, a relational database for chromosome reconstruction (1992)

In the contig mapping and analysis package, CMAP, we provide a foundation for reverse genetics by organizing information about DNA fragments obtained from an organism's genome into a physical map. The user can store information about a particular segment of DNA. This information can be both descriptive, such as any genes contained in a particular DNA fragment, or experimental, such as hybridization profiles or restriction digest patterns for comparison with other fragments. The package can then be instructed to update the physical map or provide information on a DNA fragment within the map, such as its location. The user interface is designed to minimize the learning curve associated with database usage, while eliminating the possibility of entering data outside the ranges of fields through error-checking protocols. Queries are currently accomplished by the use of dynamic SQL (structured query language), which gives the user the ability to build queries based on any combination of the attributes contained within the database without requiring that all possible queries be permanently programmed within the query software. In order to eliminate the need for knowledge of SQL, an interface was designed to allow users to build queries by menu choices. Thus, CMAP is a software package supporting a database for both the production and storage of a physical map as well as being the first step toward the production of a physical mapping workstation.
Effects of Computer-based Clinical Decision Support Systems on Clinician Performance and Patient Outcome: A Critical Appraisal of Research (1994)

Strong evidence suggests that some CDSSs can improve physician performance. Additional well-designed studies are needed to assess their effects and cost-effectiveness, especially on patient outcomes.
2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension (2015)

The ESC/ERS Guidelines represent the views of the ESC and ERS and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC and ERS are not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC/ERS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC/ERS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC/ERS Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC/ERS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.
The Application of Picture Coding Techniques to Viewdata (1980)

In March 1980 the British Post Office described research that has led to a facility for inserting high quality coloured pictures in viewdata pages. The technique is to use picture coding technology (originally devised for surveillanrce and teleconferencing) to reduce the number of bits required so that the use of low bandwidth circuits is feasible. This paper gives further technical details and describes some possible applications. A brief account of the current state of viewdata activities in the UK is included to explain why this development is regarded as important.
Elastic Wave Field Extrapolation: Redatuming of Single- and Multi-Component Seismic Data (1989)

Introduction. I. Acoustic Waves. Introduction. Acoustic wave equation. Spherical wave solutions of the acoustic two-way wave equation. Plane wave solutions of the acoustic two-way wave equation. References. II. Elastic Waves. Introduction. Elastic wave equation. Spherical wave solutions of the elastic two-way wave equation. Plane wave solutions of the elastic two-way wave equation. References. III. Acoustic Two-Way and One-Way Wave Equations. Introduction. Acoustic wave equations for horizontally layered media. Acoustic wave equations for arbitrarily inhomogeneous media. References. IV. Elastic Two-Way and One-Way Wave Equations. Introduction. Elastic wave equations for horizontally layered media. Elastic wave equations for arbitrarily inhomogeneous media. References. V. Acoustic Forward Wave Field Extrapolation. Introduction. Acoustic reciprocity theorems. Acoustic representation theorems. Acoustic two-way and one-way Rayleigh integrals. Acoustic forward wave field extrapolation operators. References. VI. Elastic Forward Wave Field Extrapolation. Introduction. Elastic reciprocity theorems. Elastic representation theorems. Elastic two-way and one-way Rayleigh integrals. Elastic forward wave extrapolation operators. References. VII. Acoustic Inverse Wave Field Extrapolation in Low Contrast Media. Introduction. Acoustic inverse wave field extrapolation in laterally invariant media. Acoustic inverse wave field extrapolation in arbitrarily inhomogeneous media. References. VIII. Elastic Inverse Wave Field Extrapolation in Low Contrast Media. Introduction. Elastic inverse wave field extrapolation in homogeneous isotropic media. Elastic inverse wave field extrapolation in arbitrarily inhomogeneous anisotropic media. References. IX. Acoustic Inverse Wave Field Extrapolation in High Contrast Media. Introduction. Recursive acoustic inverse wave field extrapolation. Iterative acoustic inverse wave field extrapolation. X. Elastic Wave Field Extrapolation in High Contrast Media. Introduction. Recursive elastic inverse wave field extrapolation. Iterative elastic inverse wave field extrapolation. XI. Acoustic Redatuming of Single-Component Seismic Data. Introduction. Forward model for single-component seismic data. Surface related acoustic pre-processing. Acoustic redatuming. References. XII. Elastic Redatuming of Multi-Component Seismic Data. Introduction. Forward model for multi-component seismic data. Surface related elastic pre-processing. Elastic redatuming. References. Appendices. A. Matrix Notation. B. Interactions of One-Way Acoustic Wave Fields. C. Interactions of One-Way Elastic Wave Fields. Index.
Droplets Formation and Merging in Two-Phase Flow Microfluidics (2011)

Two-phase flow microfluidics is emerging as a popular technology for a wide range of applications involving high throughput such as encapsulation, chemical synthesis and biochemical assays. Within this platform, the formation and merging of droplets inside an immiscible carrier fluid are two key procedures: (i) the emulsification step should lead to a very well controlled drop size (distribution); and (ii) the use of droplet as micro-reactors requires a reliable merging. A novel trend within this field is the use of additional active means of control besides the commonly used hydrodynamic manipulation. Electric fields are especially suitable for this, due to quantitative control over the amplitude and time dependence of the signals, and the flexibility in designing micro-electrode geometries. With this, the formation and merging of droplets can be achieved on-demand and with high precision. In this review on two-phase flow microfluidics, particular emphasis is given on these aspects. Also recent innovations in microfabrication technologies used for this purpose will be discussed.
Xampling: Analog to Digital at Sub-Nyquist Rates (2009)

We present a sub-Nyquist analog-to-digital converter of wideband inputs. Our circuit realizes the recently proposed modulated wideband converter, which is a flexible platform for sampling signals according to their actual bandwidth occupation. The theoretical work enables, for example, a sub-Nyquist wideband receiver, which has no prior information on the transmitter carrier positions. Our design supports input signals with 2 GHz Nyquist rate and 120 MHz spectrum occupancy, with arbitrary transmission frequencies. The sampling rate is as low as 280 MHz. To the best of our knowledge, this is the first reported wideband hardware for sub-Nyquist conversion. Furthermore, the modular design is proven to compete with state-of-the-art Nyquist ADCs in terms of resolution bits and full-scale range. We describe the various circuit design considerations, with an emphasis on the nonordinary challenges the converter introduces: mixing a signal with a multiple set of sinusoids, rather than a single local oscillator, and generation of highly-transient periodic waveforms, with transient intervals on the order of the Nyquist rate. A series of hardware experiments validates the design and demonstrate sub-Nyquist sampling.
Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor (1992)

Therapeutic ApplicationsAcute Neutropenia after Myelotoxic Anticancer TherapyThe administration of a colony-stimulating factor after standard-dose chemotherapy may be either prophylactic (i.e., given to prevent infectious complications) or therapeutic (i.e., given to patients in whom fever develops while they have neutropenia). Except in experimental treatment approaches for myeloid neoplasms, the administration of a colony-stimulating factor should not immediately precede or overlap with cytotoxic therapy, because the cycling of hematopoietic progenitor cells stimulated by the factor may increase their sensitivity to cytotoxic drugs, thus increasing rather than reducing the myelotoxicity of the cytotoxic agent.85 , 86 A theoretical precaution relates to the observation . . .
New Organic Crystals for Pulse Shape Discrimination (2009)

Efficient, readily-available, low-cost, high-energy neutron detectors can play a central role in detecting illicit nuclear weapons since neutrons are a strong indication for the presence of fissile material such as Plutonium and Highly-Enriched Uranium. The main challenge in detecting fast neutrons consists in the discrimination of the signal from the gamma radiation background. At present, the only well-investigated organic crystal scintillator for fast neutron detection, in a n/gamma mixed field, is stilbene, which while offering good pulse shape discrimination, is not widely used because of its limited availability and high cost.
An underactuated robot with a hyper-articulated deployable arm working inside an aircraft wing-box (2005)

We propose a novel concept for the actuation of a hyper-articulated robot arm for assembly operations inside an aircraft wing-box. The wing-box has a large span, but is only accessible through multiple small portholes along its length. The arm should be compact enough to enter the wing-box through the small portholes, yet capable of subsequent reconfiguration so as to access a number of assembly points inside the wing-box. Traditional electromechanical actuators powering individual joints are unsuitable for our purpose, because of limited space and large payload requirements. We propose an underactuated system which uses a single actuator at the base for the deployment of a multi d.o.f. serial linkage structure. Our proposed system exploits gravitational and gyroscopic torques in the system dynamics to rapidly deploy the system. We develop a methodology for determining the input required for a desired output trajectory and verify the results through simulation.
Crystal Structures of Hydrophobin HFBII in the Presence of Detergent Implicate the Formation of Fibrils and Monolayer Films (2007)

Hydrophobins are small, amphiphilic proteins secreted by filamentous fungi. Their functionality arises from a patch of hydrophobic residues on the protein surface. Spontaneous self-assembly of hydrophobins leads to the formation of an amphiphilic layer that remarkably reduces the surface tension of water. We have determined by x-ray diffraction two new crystal structures of Trichoderma reesei hydrophobin HFBII in the presence of a detergent. The monoclinic crystal structure (2.2A resolution, R = 22, R(free) = 28) is composed of layers of hydrophobin molecules where the hydrophobic surface areas of the molecules are aligned within the layer. Viewed perpendicular to the aligned hydrophobic surface areas, the molecules in the layer pack together to form six-membered rings, thus leaving small pores in the layer. Similar packing has been observed in the atomic force microscopy images of the self-assembled layers of class II hydrophobin, indicating that the crystal structure resembles that of natural hydrophobin film. The orthorhombic crystal structure (1.0 A resolution, R = 13, R(free) = 15) is composed of fiber-like arrays of protein molecules. Rodlet structures have been observed on amphiphilic layers formed by class I hydrophobins; fibrils of class II hydrophobins appear by vigorous shaking. We propose that the structure of the fibrils and/or rodlets is similar to that observed in the crystal structure.