gebhart/patrepeval huggingface dataset:
Fibrinolysis in normal plasma and blood: evidence for significant mechanisms independent of the plasminogen-plasmin system (1976)

Fibrinolytic activity of normal plasma and blood has been measured by 125l-fibrin solid phase assay. Activity of plasma is not affected by removal of plasminogenplasmin by affinity chromatography. Activities of euglobulin and pseudoglobulin fractions are approximately equal. epsilon-aminocaproic acid (EACA) (10 mM), tranexamic acid (10 mM), diisopropylfluorophosphate (DFP, 50 mM), and soybean and lima bean trypsin inhibitors (100 mug/ml) do not inhibit plasma activity at concentrations that inhibit pure plasmin and urokinase-activated plasma. Activity is not affected by glass contact and is not inhibited by inhibitors of contact or enzymatic activation of Hageman factor (hexadimethrine bromide, 100 mug/ml; cytochrome C, 250 mug/ml; spermidine, 2 mM; phenylmethylsulfonylfluoride, 1 mM). It is inhibited partially (30%-40%) by heating (56 degrees C, 30 min) and by zymosan (2.5 mg/ml; 40%-90% inhibition), and is increased by hydrazine (20 mM), salicylaldoxime (20 mM), DFP (50 mM), and tosyl-L-arginine methyl ester (TAMe, 10 mM)-the latter two at concentrations known to inhibit Cls of the classic, and factor D of the alternate complement pathways. Increase fibrinolytic activity with TAMe is associated with reciprocal decrease in classic and alternate complement pathway activity. It is concluded that normal plasma fibrinolytic activity is relatively independent of plasmin as the ultimate fibrinolytic enzyme, that Hageman factor-dependent pathways are of minor importance, and that significant heat-stable and heat-labile nonplasmin fibrinolytic activities are operative. These may include proteinases involved in complement activation, and in common control of classic and alternate complement pathways, as well as other nonplasmin proteinases.
Pharmacologic activity and pharmacokinetics of metabolites of regorafenib in preclinical models (2016)

Regorafenib is an orally administered inhibitor of protein kinases involved in tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment. Phase III studies showed that regorafenib has efficacy in patients with advanced gastrointestinal stromal tumors or treatment-refractory metastatic colorectal cancer. In clinical studies, steady-state exposure to the M-2 and M-5 metabolites of regorafenib was similar to that of the parent drug; however, the contribution of these metabolites to the overall observed clinical activity of regorafenib cannot be investigated in clinical trials. Therefore, we assessed the pharmacokinetics and pharmacodynamics of regorafenib, M-2, and M-5 in vitro and in murine xenograft models. M-2 and M-5 showed similar kinase inhibition profiles and comparable potency to regorafenib in a competitive binding assay. Inhibition of key target kinases by all three compounds was confirmed in cell-based assays. In murine xenograft models, oral regorafenib, M-2, and M-5 significantly inhibited tumor growth versus controls. Total peak plasma drug concentrations and exposure to M-2 and M-5 in mice after repeated oral dosing with regorafenib 10 mg/kg/day were comparable to those in humans. In vitro studies showed high binding of regorafenib, M-2, and M-5 to plasma proteins, with unbound fractions of ~0.6%, ~0.9%, and ~0.4%, respectively, in murine plasma and ~0.5%, ~0.2%, and ~0.05%, respectively, in human plasma. Estimated free plasma concentrations of regorafenib and M-2, but not M-5, exceeded the IC<sub>50</sub> at human and murine VEGFR2, suggesting that regorafenib and M-2 are the primary contributors to the pharmacologic activity of regorafenib in vivo.
Development of Multiexon Skipping Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy (2013)

Duchenne muscular dystrophy (DMD) is an incurable, X-linked progressive muscle degenerative disorder that results from the absence of dystrophin protein and leads to premature death in affected individuals due to respiratory and/or cardiac failure typically by age of 30. Very recently the exciting prospect of an effective oligonucleotide therapy has emerged which restores dystrophin protein expression to affected tissues in DMD patients with highly promising data from a series of clinical trials. This therapeutic approach is highly mutation specific and thus is personalised. Therefore DMD has emerged as a model genetic disorder for understanding and overcoming of the challenges of developing personalised genetic medicines. One of the greatest weaknesses of the current oligonucleotide approach is that it is a mutation-specific therapy. To address this limitation, we have recently demonstrated that exons 45-55 skipping therapy has the potential to treat clusters of mutations that cause DMD, which could significantly reduce the number of compounds that would need to be developed in order to successfully treat all DMD patients. Here we discuss and review the latest preclinical work in this area as well as a variety of accompanying issues, including efficacy and potential toxicity of antisense oligonucleotides, prior to human clinical trials.
Design of an interactive lumbar puncture simulator with tactile feedback (2002)

A computer-based simulation utilizing high-resolution 3D graphics and a force-feedback device to train students and/or residents in limiter puncture is discussed. The simulator consists of a combination of specialized hardware, custom software running on a high-resolution graphics workstation. The hardware under development for this project is described. The major piece of specialized hardware is the force-feedback needle simulator. Position sensors track the insertion angle or trajectory of the device, while a programmable motor or actuator provides variable resistance to insertion, depending upon which simulated anatomic structures the virtual needle is penetrating. Thus, the student may place the virtual needle at the desired angle and will feel realistic resistance while inserting. If an incorrect trajectory is used and bone is contacted, the resulting sudden sharp increase in resistance would be conveyed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Assurer la perennite de l'approvisionnement en eau en milieu rural : recommandations issues d'une etude mondiale (1997)

This study found that employing a demand-responsive approach at the community level significantly increases the likelihood of water system sustainability. However, it also found that even projects that have adopted this approach tend to apply it inconsistently among the communities where they work. The study found that to be effective, a demand-responsive approach should include procedures for an adequate flow of information to households, provisions for capacity-building at all levels, and a re-orientation of supply agencies to allow consumer demand to guide investment programs. The study also found that the existence of a formal organization to manage the water system and training of household members are significant factors in ensuring water system sustainability. Positive correlation were also found between water system sustainability and water committee training in operations and maintenance, and the quality of construction of the system and water system sustainability, although these findings are less consistent across countries.
Analysis of planar sandwich inductors by current images (1990)

Inductors with spiral windings sandwiched between top- and bottom-plane thick magnetic plates are investigated theoretically using the method of current images. Expressions are obtained for the inductances, and magnetic fields of these planar structures assuming infinite plane thicknesses. The dependence of the inductance on the permeability and the distances between the spiral windings and the top and bottom plates is studied by numerically evaluating the inductance expressions. It is shown that, except for some limiting cases, the inductance depends only on the net distance between the top and bottom magnetic plates and is independent of the position of the spiral windings within the gap. Furthermore, it is found that, in contrast to open planar structures, the sandwich inductor can yield large values of inductances with the enhancement over air-core values limited only by the permeability of the magnetic plates. Numerical evaluation of the formulas for magnetic fields both inside the magnetic plates and in the gap are used to calculate energy density variation in the device, to estimate lateral dimensions of these sandwich inductors, to discuss construction of multiple devices in a single-sandwich structure, and to discuss calculation of losses in the sandwich inductors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
The speech transcoding frame 2000 for GSM cellular systems (2002)

The Global System for Mobile Communications (GSM) is the leading digital mobile telephone standard in the world. This paper describes the GSM cellular system, its features and services, and its system architecture. It also details the Speech Transcoding Frame (STF) 2000, one component of Lucent Technologies' GSM system. The STF 2000, which provides speech encoding and decoding (known collectively as “transcoding”) and data rate adaptation, is cost effective, with a flexible, modular architecture that allows gradual system growth and enhancements with little or no downtime. It has the capability for “half-rate” speech coding, which enables network operators to double their over-the-air capacity without the need for increased radio-frequency (RF) spectrum. The system includes a notebook PC with a graphical user interface that simplifies installation, maintenance, and on-site diagnostics. Fault-recovery software enables the STF 2000 to recover automatically from internally and externally detected faults. Redundancy is built into critical system components so that standby or spare components can be switched into service when there is a fault in the active component. GSM features such as discontinuous transmission increase the system efficiency by decreasing radio interference and saving battery power at mobile stations. The STF 2000 meets European telecommunications standards.
New criteria for placement of a prophylactic vena cava filter. (1986)

In order to identify patients who, having had an initial pulmonary embolism, are likely to develop recurrent emboli despite adequate anticoagulation therapy, ten patients (group 1) with documented recurrent pulmonary embolism during anticoagulation therapy were compared with 31 patients (group 2) who showed no evidence of recurrent emboli during the treatment period. Risk factors for thromboembolic disease were similar between the two groups. Noninvasive venous studies of the lower extremities, including Doppler venous ultrasound and phleborheography (PRG), were performed upon all patients after the initial embolic event. Of the ten patients in group 1, seven (70 per cent) had clinical signs of deep vein thrombosis (DVT). Doppler studies were positive for eight of the nine patients studied, and PRG studies were positive for eight of eight patients tested. In contrast, of the 31 patients who responded well to medical therapy, one patient (3 per cent) had clinical signs of DVT, three patients (10 per cent) had positive Doppler studies and one patient (3 per cent) had a positive PRG. Combined Doppler and PRG studies were positive in 100 per cent of the patients in group 1 but in only 6 per cent of the patients in group 2 (p less than 0.001). The results of this study suggest that patients having an initial pulmonary embolism and DVT of sufficient extent detected by noninvasive studies may be at an increased risk for recurrent PE despite anticoagulation therapy. Insertion of a vena cava filter should be considered in these patients prior to the second embolic event.
The Power and Efficiency Limits of Piezoelectric Energy Harvesting (2013)

The fundamental limits of cantilevered piezoelectric energy harvesters have not been well established. As with any other power generation technology, it is critical to establish the limits of power output and efficiency. Mathematical models for piezoelectric energy harvester power output have seen continued refinement, but these models have mainly been used and compared to individual harvester designs. Moreover, existing models all assume power scales with acceleration input, and take no account for the upper limit of the acceleration due to the ultimate strength of the piezoelectric material. Additionally, models for efficiency have been developed, but the limits have not been thoroughly explored. In this paper, we present the upper limits of input acceleration and output power for a piezoelectric harvester device. We then use these expressions, along with a previously developed ideal design method, to explore the upper limits of power production across a range of system masses and excitation frequencies. We also investigate general efficiency limits of these devices. We show the upper limit using an existing model and develop an alternate model that is applicable to excitation sources that are not capable of energy recovery.
PATHOGENESIS OF OEDEMA OF THE OPTIC DISC (PAPILLOEDEMA): A PRELIMINARY REPORT (1964)

I HAVE used the term "oedema of the optic disc" instead of the conventional "papilloedema" because the term "papilloedema" originated from an erroneous impression that the normal optic disc was elevated like a papilla. Since the structure is usually flat, the term is a misnomer. It must, however, be conceded that there are considerable variations in the appearance of the disc, all of which may be "within physiological limits". For instance, it is not uncommon to encounter a pronounced prominence of the disc mainly at its upper and lower poles, accompanied by a forward curving of the branches of the central artery of the retina and the tributaries of the central vein of the retina. The so-called "pseudo-papilloedema", in which the entire disc is prominent and the edges obscured, typically (although not invariably) associated with a high degree of hypermetropia is more rare. It is also noteworthy that the so-called physiological depression may vary considerably in size or indeed may be entirely absent. Furthermore, although the colour of the normal disc is described as being pink, it may show relative pallor especially in high myopes and in elderly people.
The effect of consistency on cache response time (2000)

This report analyzes the impact of cache consistency on the response time of client requests. The analysis divides cache responses into classes according to whether or not the cache communicated with a remote server and whether or not object data was served from the cache. Analysis of traces from deployed proxy cache servers demonstrates that a round-trip to a remote server is the dominant factor for response time. This study concludes that improving cache consistency will reduce response time and allow a cache to serve more user requests.
The influence of microstructure and monomer properties on the erosion mechanism of a class of polyanhydrides (1993)

Abstract The erosion of three different polyanhydrides consisting of sebacic acid (SA) and 1,3‐bis( p ‐carboxyphenoxy)propane (CPP) was investigated. Melt cast polymer matrices were prepared from the homopolymer p (SA) and two copolymers, p (CPP‐SA) 20 : 80 and p (CPP‐SA) 50 : 50. Particular attention was paid to the influence of the polymer matrix microstructure and of the monomers on erosion. Using polarized light microscopy we found that p (SA) and p (CPP‐SA) 20 : 80 matrices consist of spherulites. SEM investigations showed that their crystalline parts are more resistant to erosion than their amorphous areas. The matrices erode into highly porous devices, whose porosity is detectable by mercury porosimetry. Using wide‐angle x‐ray diffractometry we found that monomers crystallize inside the pores. DSC investigations showed a maximum of crystallized SA after 2–6 days and a continuous increase of CPP, which stays in the devices for weeks. We conclude that the microstructure and the monomer properties are the two main factors which determine the erosion of these polymers. The obtained data on changes in porosity, crystallinity, polymer matrix thickness, erosion front velocities, crystalline monomer content, and monomer release provides the basis for quantitatively describing the erosion process. © 1993 John Wiley & Sons, Inc.
Improved Vectors for Selecting Resistance to Hygromycin (1994)

Resistance to hygromycin B is an important dominant selectable marker in fungal transformation. Our goal was to improve vectors for hygromycin selection by making the gene more compact, by eliminating sites for commonly used restriction enzymes, and by subcloning the modified gene into convenient vectors. These improvements were made by modifying pCSN43 (Staben et al. 1989 Fungal Genetics Newsl. 36:79-81) through three rounds of megaprimer mutagenesis (Aiyar and Leis, 1993 Biotechniques 14:366-368 ), a technique based on polymerase chain reaction amplification. Plasmid pCSN43 has a 2.4 kb SalI fragment containing the bacterial hph gene (Gritz and Davies, 1983 Gene 25:179-188), encoding hygromycin B phosphotransferase, under control of the Aspergillus nidulans trpC promoter and terminator (Mullaney et al. 1985 MGG 199:37-45)
Elastic Site: Using Clouds to Elastically Extend Site Resources (2010)

Infrastructure-as-a-Service (IaaS) cloud computing offers new possibilities to scientific communities. One of the most significant is the ability to elastically provision and relinquish new resources in response to changes in demand. In our work, we develop a model of an “elastic site” that efficiently adapts services provided within a site, such as batch schedulers, storage archives, or Web services to take advantage of elastically provisioned resources. We describe the system architecture along with the issues involved with elastic provisioning, such as security, privacy, and various logistical considerations. To avoid over- or under-provisioning the resources we propose three different policies to efficiently schedule resource deployment based on demand. We have implemented a resource manager, built on the Nimbus toolkit to dynamically and securely extend existing physical clusters into the cloud. Our elastic site manager interfaces directly with local resource managers, such as Torque. We have developed and evaluated policies for resource provisioning on a Nimbus-based cloud at the University of Chicago, another at Indiana University, and Amazon EC2. We demonstrate a dynamic and responsive elastic cluster, capable of responding effectively to a variety of job submission patterns. We also demonstrate that we can process 10 times faster by expanding our cluster up to 150 EC2 nodes.
Induction motor rotor bar damage evaluation with magnetic field analysis (2015)

Detection of defects in induction machine rotor bars for unassembled motors is required to evaluate machines considered for repair as well as fulfilling incremental quality assurance checks in the manufacture of new machines. Detection of rotor bar defects prior to motor assembly are critical in increasing repair efficiency and assuring the quality of newly manufactured machines. Many methods of detecting rotor bar defects in unassembled motors lack the sensitivity to find both major and minor defects in both cast and fabricated rotors along with additional deficiencies in quantifiable test results and arc-flash safety hazards. A process of direct magnetic field analysis can examine measurements from induced currents in a rotor separated from its stator yielding a high-resolution fingerprint of a rotor's magnetic field. This process identifies both major and minor rotor bar defects in a repeatable and quantifiable manner appropriate for numerical evaluation without arc-flash safety hazards.
Assay of Catechol-O-Methyltransferase Activity in Human Erythrocytes Using Norepinephrine as a Natural Substrate (2002)

The established assay method used to assess S- and MB-COMT activities in human erythrocytes could be useful to elucidate catecholamine metabolism in the normal physiological state as well as in the pathology of certain diseases.
The A-ring reduction of 11-ketotestosterone is efficiently catalysed by AKR1D1 and SRD5A2 but not SRD5A1 (2020)

Testosterone and its 5α-reduced form, 5α-dihydrotestosterone, were previously thought to represent the only active androgens in humans. However, recent studies have shown that the potent androgen, 11-ketotestosterone, derived from the adrenal androgen precursor, 11β-hydroxyandrostenedione, may in fact serve as the primary androgen in healthy women. Yet, despite recent renewed interest in these steroids, their downstream metabolism has remained undetermined. We therefore set out to investigate the metabolism of 11-ketotestosterone by characterising the 5α- or 5β-reduction commitment step. We show that inactivation of 11-ketotestosterone is predominantly driven by AKR1D1, which efficiently catalyses the 5β-reduction of 11-ketotestosterone, committing it to a metabolic pathway that terminates in 11-ketoetiocholanolone. We demonstrate that 5α-reduction of 11-ketotestosterone is catalysed by SRD5A2, but not SRD5A1, and terminates in 11-ketoandrosterone, but is only responsible for a minority of 11-ketotestosterone inactivation. However, as 11-ketoetiocholanolone is also generated by the metabolism of the glucocorticoid cortisone, 11-ketoandrosterone should be considered a more specific urinary marker of 11-ketotestosterone production.
Switching Kinetics of Pb(Zr, Ti)O<sub>3</sub> Thin Films Grown by Chemical Vapor Deposition (1993)

The pulse switching kinetics of ferroelectric Pb(Zr, Ti)O 3 thin films grown by chemical vapor deposition (CVD) has been investigated. The switching time was proven to be proportional to the electrode area of the thin-film capacitor under our measurement conditions. Polarization switching was also characterized by the exponential functions of reciprocal voltage. On the basis of the experimental results, the relationships among the apparent switching phenomena, the nucleation process of reversed domains and the time constant of the measurement system are discussed. Moreover, the switching time determined by the low nucleation rate is formulated.
Mutation of nucleotides around the +1 position of type 3 polymerase III promoters: The effect on transcriptional activity and start site usage (2017)

Type 3 RNA polymerase III (Pol III) promoters are widely used for the expression of small RNAs such as short hairpin RNA and guide RNA in the popular RNAi and CRISPR-Cas gene regulation systems. Although it is generally believed that type 3 Pol III promoters use a defined transcription start site (+1 position), most man-made promoter constructs contain local sequence alterations of which the impact on transcription efficiency and initiation accuracy is not known. For three human type 3 Pol III promoters (7SK, U6, and H1), we demonstrated that the nucleotides around the +1 position affect both the transcriptional efficiency and start site selection. Human 7SK and U6 promoters with A or G at the +1 position efficiently produced small RNAs with a precise +1 start site. The human H1 promoter with +1A or G also efficiently produced small RNAs but from multiple start sites in the -3/-1 window. These results provide new insights for the design of vectors for accurate expression of designed small RNAs for research and therapeutic purposes.