gebhart/patrepeval huggingface dataset:
Knee Brace Would Lock And Unlock Automatically (1995)

Proposed knee brace designed to aid rehabilitation of person who suffered some muscle damage in leg. Not limited to locking in straight-leg position and, instead, locks at any bend angle. Does not prevent knee from bearing weight. Instead, knee brace allows knee to bear weight and locks only when foot and lower leg bear weight. Thus, brace prevents flexion that wearer desired to prevent but could not prevent because of weakened muscles. Knee bends freely to exercise knee-related muscles. Knee brace strapped at upper end to leg above knee, and anchored at lower end by stirrup under foot. Joint mechanism (identical mechanisms used in left and right assemblies) allows knee joint to flex freely except when weight applied to heel.
Functional characterization of the human thiopurine <i>S</i>‐methyltransferase (TPMT) gene promoter (1998)

Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyzes S-methylation of aromatic and heterocyclic sulfhydryl compounds, including anticancer and immunosuppressive thiopurines. We recently isolated the human TPMT promoter, which does not contain TATA box or CCAAT element consensus sequences, but is GC rich with multiple GC boxes and other putative cis-regulatory elements. Here, we report the functional characterization of the TPMT promoter, revealing several positive regulatory elements and identifying stimulating protein 1 (Sp1) as an important trans-activator essential for constitutive activity in cell culture. One major and two closely located minor transcription start points were identified in HepG2 cells. Deletion analysis revealed positive cis-regulatory elements located in the regions -85 to -75, -68 to -58, -58 to -51 and +34 to +60 relative to the transcription start site. DNaseI footprinting analysis and cotransfection in Drosophila Schneider SL2 cells documented that Sp1 binds to the TPMT promoter and is important for constitutive activity. We conclude that constitutive transcription of the TPMT gene involves a limited upstream GC-rich DNA sequence, containing multiple GC boxes, and that transcription factor Sp1 [or related protein(s)] is an important trans-activator of this TATA-less promoter.
A simulation study of ventricular rate smoothing during atrial fibrillation (2004)

Ventricular rate smoothing (VRS) algorithms have been proposed to regularize ventricular response during atrial fibrillation (AF) in order to improve patient's symptoms and hemodynamics. In the present study, we conduct computer simulations to evaluate the performance of a new VRS algorithm based on a quantitative AF model. The results of this study show that the new VRS algorithm can effectively suppress the irregularity of the ventricular responses during AF without unnecessary high-rate ventricular pacing. Moreover, the percentage of ventricular paces is limited while many ventricular senses with normal rhythm and rate are preferably preserved.
App-Bisect: autonomous healing for microservice-based apps (2015)

The microservice and DevOps approach to software design has resulted in new software features being delivered immediately to users, instead of waiting for long refresh cycles. On the downside, software bugs and performance regressions have now become an important cause of downtime. We propose app-bisect, an autonomous tool to troubleshoot and repair such software issues in production environments. Our insight is that the evolution of microservices in an application can be captured as mutations to the graph of microservice dependencies, such that a particular version of the graph from the past can be deployed automatically, as an interim measure until the problem is permanently fixed. Using canary testing and version-aware routing techniques, we describe how the search process can be sped up to identify such a candidate version. We present the overall design and key challenges towards implementing such a system.
Novel Human Urate Transporter 1 Inhibitors as Hypouricemic Drug Candidates with Favorable Druggability (2020)

Lesinurad, a human urate transporter 1 (URAT1) inhibitor approved as a medication for the treatment of hyperuricemia associated with gout in 2015, can cause liver and renal toxicity. Here, we modified all three structural components of lesinurad by applying scaffold hopping, bioisosterism, and substituent-decorating strategies. In a mouse model of acute hyperuricemia, 21 of the synthesized compounds showed increased serum uric acid (SUA)-reducing activity; SUA was about 4-fold lower in animals treated with <b>44</b>, <b>54</b>, and <b>83</b> compared with lesinurad or benzbromarone. In the URAT1 inhibition assay, <b>44</b> was over 8-fold more potent than lesinurad (IC<sub>50</sub>: 1.57 μM <i>vs</i> 13.21 μM). Notably, <b>83</b> also displayed potent inhibitory activity (IC<sub>50</sub> = 31.73 μM) against GLUT9. Furthermore, we also preliminarily explored the effect of chirality on the potency of the promising derivatives <b>44</b> and <b>54</b>. Compounds <b>44</b>, <b>54</b>, and <b>83</b> showed favorable drug-like pharmacokinetics and appear to be promising candidates for the treatment of hyperuricemia and gout.
Phosphatidylcholine synthesis is elevated in neuronal models of Gaucher disease due to direct activation of CTP:phosphocholine cytidylyltransferase by glucosylceramide (2002)

Glucosylceramide (GlcCer) accumulates in the inherited metabolic disorder, Gaucher disease, because of the defective activity of lysosomal glucocerebrosidase. We previously demonstrated that upon GlcCer accumulation, cultured hippocampal neurons exhibit modified growth patterns, altered endoplasmic reticulum density, and altered calcium release from intracellular stores. We here examined the relationship between GlcCer accumulation and phospholipid synthesis. After treatment of neurons with an active site-directed inhibitor of glucocerebrosidase, or in neurons obtained from a mouse model of Gaucher disease, [14C]methyl choline incorporation into [14C]phosphatidylcholine ([14C]PC) and [14C]sphingomyelin was elevated, as were [14C]CDP-choline levels, suggesting that CTP:phosphocholine cytidylyltransferase (CCT) is activated. Indeed, CCT activity was elevated in neurons that had accumulated GlcCer. GlcCer, but not galactosylceramide (GalCer), stimulated CCT activity in rat brain homogenates, and significantly higher levels of CCT were membrane associated in cortical homogenates from a mouse model of Gaucher disease compared with wild-type mice. Because CCT mRNA and protein levels were unaltered in either neurons or brain tissue that had accumulated GlcCer, it appeared likely that GlcCer activates CCT by a post-translational mechanism. This was verified by examination of the effect of GlcCer on CCT purified about 1200-fold from rat brain. GlcCer stimulated CCT activity, with stimulation observed at levels as low as 2.5 mol% and with maximal activation reached at 10 mol%. In contrast, GalCer had no effect. Together, these data demonstrate that GlcCer directly activates CCT, which results in elevated PC synthesis, which may account for some of the changes in growth rates observed upon neuronal GlcCer accumulation.
Fiber probe based microfluidic raman spectroscopy (2010)

We report a novel fiber probe based Raman detection system on a microfluidic platform where a split Raman probe is directly embedded into a polydimethylsiloxane (PDMS) chip. In contrast to previous Raman detection schemes in microfluidics, probe based detection offers reduced background and portability. Compared to conventional backscattering probe designs, the split fiber probe we used in this system, results in a reduced size and offers flexibility to modify the collection geometry to minimize the background generated by the fibers. Also our microfluidic chip design enables us to obtain an alignment free system. As a proof of concept we demonstrate the sensitivity of the device for urea detection at relevant human physiological levels with a low acquisition time. The development of this system on a microfluidic platform means portable, lab on a chip devices for biological analyte detection and environmental sensing using Raman spectroscopy are now within reach.
Highly Active Ruthenium Metathesis Catalysts Exhibiting Unprecedented Activity and <i>Z</i>-Selectivity (2013)

A novel chelated ruthenium-based metathesis catalyst bearing an N-2,6-diisopropylphenyl group is reported and displays near-perfect selectivity for the Z-olefin (>95%), as well as unparalleled TONs of up to 7400, in a variety of homodimerization and industrially relevant metathesis reactions. This derivative and other new catalytically active species were synthesized using an improved method employing sodium carboxylates to induce the salt metathesis and C-H activation of these chelated complexes. All of these new ruthenium-based catalysts are highly Z-selective in the homodimerization of terminal olefins.
A high-speed truly random number generator based on an autonomous chaotic oscillator (2014)

A truly random number generator based on an autonomous bipolar-transistor cross-coupled chaotic oscillator is introduced. The effect of noise on the chaotic trajectory is analyzed. Inclusion of noise renders generated bits unpredictable, qualifying the proposed chaos based generator to be used as a truly random source. Simulation and experimental results verifying the feasibility and correct operation of the circuit are given such that generated bits fulfill NIST-800-22 statistical test suite without post-processing. Presented circuit features much higher and constant throughput rates and allows for offset compensation.
Thermodynamic treatment of oligonucleotide duplex–simplex equilibria (2003)

Thermodynamic formulations have been devised to obtain Delta G degrees values directly from spectroscopic data at a fixed common temperature in nucleic acid duplex-simplex melting curves. In addition, the dependence of melting on salt concentration has been expressed in terms of a stepwise stoichiometric representation, which leads to a specific equation for the partition of the added sodium ions between the different oligonucleotide forms.
Design, Synthesis, and Antiviral Evaluations of 1-(Substituted benzyl)-2-substituted-5,6-dichlorobenzimidazoles as Nonnucleoside Analogues of 2,5,6-Trichloro-1-(β-<scp>d</scp>-ribofuranosyl)benzimidazole (1998)

We have recently reported that certain ribosylated polyhalogenated benzimidazoles are potent and selective inhibitors of HCMV replication at noncytotoxic concentrations. To extend the structure-activity relationship beyond these first-generation compounds, we alkylated 5,6-dichloro-2-substituted-benzimidazoles with either a series of substituted benzyl halides or (2-bromoethyl)benzene to obtain five series of nonnucleoside analogues. Evaluation of these compounds for activity against herpes viruses revealed that the new compounds were less active than the benzimidazole ribonucleosides against human cytomegalovirus (HCMV) and inactive against herpes simplex virus type 1 (HSV-1). However, as part of our broader antiviral testing, we found that some of these compounds were active against HIV. Comparisons of the biological data revealed that a chloro or bromo group was required at the 2-position for the best separation of activity against HIV and cytotoxicity. Evaluation of the most active compounds against drug-resistant HIV suggested that they act by a mechanism other than inhibition of reverse transcriptase.
Terahertz metamaterial devices (2007)

Compared to the neighboring infrared and microwave regions, the terahertz regime is still in need of fundamental technological advances. This derives, in part, from a paucity of naturally occurring materials with useful electronic or photonic properties at terahertz frequencies. This results in formidable challenges for creating the components needed for generating, detecting, and manipulating THz waves. Considering the promising applications of THz radiation, it is important overcome such material limitations by searching for new materials, or by constructing artificial materials with a desired electromagnetic response. Metamaterials are a new type of artificial composite with electromagnetic properties that derive from their sub-wavelength structure. The potential of metamaterials for THz radiation originates from a resonant electromagnetic response which can be tailored for specific applications. Metamaterials thus offer a route towards helping to fill the so-called "THz gap". In this work we discuss novel planar THz metamaterials. Importantly, the dependence of the resonant response on the supporting substrate enables the creation of active THz metamaterials. We show that the resonant response can be efficiently controlled using optical or electrical approaches. This has resulted in the creation of efficient THz switches and modulators of potential importance for advancing numerous real world THz applications.
Pancreatic stem cells: a therapeutic agent that may offer the best approach for curing type 1 diabetes (2001)

Type 1 (insulin-dependent) diabetes is one of the most costly chronic diseases of children and adolescents in North America and Europe. It occurs in genetically predisposed individuals when the immune system attacks and destroys specifically the insulin-producing beta cells of the pancreatic islets of Langerhans. Although routine insulin injections can provide diabetic patients their daily insulin requirements, non-compliance commonly results in blood glucose excursions that eventually lead to microvascular and macrovascular complications and early death. The only real 'cure' for type 1 diabetes is replacement of the beta-cell mass which, today, is either an ectopancreatic transplant or an islet of Langerhans implant. Two new developments may offer additional options: surrogate, non-endocrine cells genetically modified to secrete insulin in response to high blood glucose levels; and stem cells that possess the capacity to differentiate to endocrine pancreas. In this short review, we discuss the efforts currently being made to regulate pancreatic stem cell growth in order to produce large numbers of functional islets that can be used as implants. Hopefully, autologous stem cell-derived islet cell implants without lifelong immunosuppressive therapy may one day be realized.
Apolipoprotein C-II: the re-emergence of a forgotten factor (2020)

The role of apoC-II in TG metabolism is reviewed, as well as recent efforts to develop apoC-II mimetic peptides into a novel therapy for HTG.
Degradation of Ochratoxin A by <i>Brevibacterium</i> Species (2011)

The ability to degrade ochratoxin A was studied in different bacteria with a well-known capacity to transform aromatic compounds. Strains belonging to Rhodococcus, Pseudomonas, and Brevibacterium genera were grown in liquid synthetic culture medium containing ochratoxin A. Brevibacterium spp. strains showed 100% degradation of ochratoxin A. Ochratoxin α was detected and identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) as a degradation product in the cell-free supernatants. The degradation of ochratoxin A is of public concern for food and environmental safety, because it could contribute to the development of new biological ochratoxin A detoxification systems in foodstuffs. In this study, the degradation of ochratoxin A by bacteria belonging to the food chain was demonstrated for the first time.
Large P−P Distance Diphosphines and Their Monophosphine Analogues as Ligands in the Palladium-Catalyzed Telomerization of 1,3-Butadiene and Methanol (2011)

The potential of diphosphines based on a dibenzodioxocin or benzofurobenzofuran backbone possessing large P−P distances was studied for the selective telomerization of 1,3-butadiene with methanol under commercially relevant process conditions to obtain 1-methoxyocta-2,7-diene (1-MOD). They were found to act as monophosphines. New bulky monophosphine analogues of the same backbone and ferrocene were also evaluated. Several ligands showed improved selectivity and yield compared to the benchmark ligand PPh3 and monoxantphos. Especially 1,6-bis(diphenylphosphino)-5a,10b-dihydro-5a,10b-dimethyl-3,8-dimethylbenzofuro[3,2-b]benzofuran (3) and, 2,10-di-tert-butyl-4-diphenylphosphino-6,12-methano-12H-dibenzo[2,1-d:1′,2′′-g][1,3]dioxocin (7), a diphosphine and a monophosphine, respectively, stand out as excellent ligands in terms of yield, selectivity, and stability.
Frequency‐sensitive switching control effect induced by two‐photon resonance in an EIT‐based layered medium (2013)

The optical response of an atomic vapor can be coherently manipulated by tunable quantum interference occurring in atomic transition processes. A periodic layered medium whose unit cells consist of a dielectric and an EIT (electromagnetically induced transparency) atomic vapor is designed for light propagation manipulation. Such an EIT‐based periodic layered medium exhibits a flexible frequency‐sensitive optical response, where a very small change in probe frequency can lead to a drastic variation of reflectance and transmittance. As the destructive quantum interference relevant to two‐photon resonance arises in EIT atoms interacting with both control and probe fields, the controllable optical processes that depend sensitively on the external control field will take place in this EIT‐based periodic layered medium. Such a frequency‐sensitive and field‐controlled optical behavior of reflection and transmission in the EIT photonic crystal can be applicable to designs of new devices such as photonic switches, photonic logic gates and photonic transistors, where one laser field can be controlled by the other one, and would have potential applications in the areas of integrated optical circuits and other related techniques (e.g., all‐optical instrumentations).
Population-Based and Personalized Design of Total Knee Replacement Prosthesis for Additive Manufacturing Based on Chinese Anthropometric Data (2020)

At present, most total knee replacement (TKR) prostheses on the market are designed according to the sizes of Caucasians. However, extensive studies have indicated that human anatomies differ among different ethnicities. A number of reports have indicated that Chinese TKR patients do not match with available prostheses. In this study, computed tomography (CT) images of 52 knees of Chinese men and women were used for anthropometric measurements. Index and geometric measurements were defined and used for correlation analysis. Key parameters from the measurement results were identified. Detailed geometries of knees were measured as coordinates. A deformable three-dimensional (3D) knee model based on anatomical coordinates correlating with the identified key parameters was generated. A prosthesis was then designed according to the analyzed results. Surface matching analysis, bone resection analysis, and cadaveric trials were conducted and compared with commercial products to validate the proposed design. The femoral component designed by this study resulted in the highest accuracy (root mean square point-to-surface (RMS PS), (1.08 ± 0.20) mm) and lowest amount of resected bone volume (27 412 mm3) in comparison with two commercial knee prostheses. This study suggests a new approach for population-based patient-specific femoral prosthesis design. With a single, easily acquired dimension—namely, epicondyle width (ECW)—as input, a patient-specific femoral prosthesis can be designed according to the analyzed measured data and manufactured by additive manufacturing (AM) methods. Meanwhile, the reconstructed femoral condylar surface was compared with the femoral condylar surface in the original CT scanning data. The average RMS PS distance of the reconstructed femoral condylar surface among all data was (1.10 ± 0.18) mm, which is comparable to other statistical shape modeling methods using multiple radiographs as input data. There is a need to develop an anthropometric-based knee prosthesis for the Chinese population. Based on the anthropometry of the Chinese population, our new design fits Chinese patients better and reserves more bone volume compared with current commercial prostheses, which is an essential step toward AM for personalized knee prostheses.
Induction of virus-producing tumours in athymic nude mice by bovine papillomavirus type 4 (1989)

Bovine papillomavirus type 4 (BPV-4), the causative agent of alimentary papillomatosis, has been used to infect, in vitro, fragments of palatine mucosa from late term bovine fetuses. These small explants were placed beneath the renal capsule of athymic nude mice where they grew to produce, at first, squamous epithelial cysts containing BPV-4 genomic DNA and, later, papillomas which were morphologically identical to those of cattle and which contained large amounts of replicating virus. The possible utility of this technique in assessing neutralising antibodies in vaccine development is discussed.
A Signature Test Framework for Rapid Production Testing of RF Circuits (2002)

Production test costs for today's RF circuits are rapidly escalating. Two factors are responsible for this cost escalation: (a) the high cost of RF ATEs and (b) long test times required by elaborate performance tests. In this paper, we propose a framework for low-cost test of RF circuits using modulation of a baseband test signal and subsequent demodulation of the DUT response. The demodulated response of the DUT is used as a signature from which all the performance specifications are predicted. The applied test signal is optimized in such a way that the error between the measured DUT performances and the predicted DUT performances is minimized. The proposed low-cost solution can be easily built into a load board that can be interfaced to an inexpensive tester.
Quantum computation with quantum dots and terahertz cavity quantum electrodynamics (1999)

A quantum computer is proposed in which information is stored in the two lowest electronic states of doped quantum dots (QD's). Many QD's are located in a microcavity. A pair of gates controls the energy levels in each QD. A controlled-NOT (C-NOT) operation involving any pair of QD's can be effected by a sequence of gate-voltage pulses which tune the QD energy levels into resonance with frequencies of the cavity or a laser. The duration of a C-NOT operation is estimated to be much shorter than the time for an electron to decohere by emitting an acoustic phonon.