gebhart/patrepeval huggingface dataset:
Studies on the mechanisms of action of aprotinin and tranexamic acid as plasmin inhibitors and antifibrinolytic agents. (1994)

Both aprotinin and tranexamic acid are effective inhibitors of fibrinolysis in vitro and in vivo and both agents can act as plasmin inhibitors in purified systems, although there is some debate on their exact mechanism of action in vivo. The studies reported here using an in vitro clot lysis system designed to provide precise inhibition constants show that aprotinin remains a very potent inhibitor of plasmin even in the presence of fibrin with Ki = 2 nM. Plasmin-aprotinin interactions in solution are not affected by a number of kringle binding ligands, aminohexanoic acid, tranexamic acid or CNBr-fibrinogen fragments with Ki = 0.4 nM. The difference between these two Ki values is explained by competition for the plasmin active site between substrate (fibrin) and inhibitor (aprotinin). Inhibition of fibrinolysis by tranexamic acid is not readily analysed by a simple inhibition model which may be due to multiple overlapping ligand-kringle interactions or tranexamic-fibrin interactions. Experiments using combinations of aprotinin and tranexamic acid in the clot lysis system confirm the complementary nature of inhibitory mechanisms and suggest a slight synergism. These results support the idea that aprotinin inhibition of plasmin is a primary mode of action in vivo, and suggest that combination therapy of aprotinin with tranexamic acid might be more effective than either inhibitor alone.
Directed Evolution of an Esterase from Pseudomonas fluorescens. Random Mutagenesis by Error-Prone PCR or a Mutator Strain and Identification of Mutants Showing Enhanced Enantioselectivity by a Resorufin-Based Fluorescence Assay (1999)

The gene encoding an esterase from Pseudomonas fluorescens (PFE) was subjected to random mutagenesis by error-prone PCR or by using the mutator strain Epicurian coli XL1-Red. Enzyme libraries were then created in microtiter plates by expression of PFE-variants in E. coli. These were assayed for improved enantioselectivity in a Beckman robot system using optically pure (R)- or (S)-3-phenylbutyric acid resorufin esters, resulting in the identification of several mutants showing up to almost two-fold enantioselectivity (E(true) = 5.2 to 6.6) compared to wild-type PFE (E(true) = 3.5).
A constrained optimization approach to virtual fixtures (2005)

We describe a new method to generate virtual fixtures for surgical robot control which provide sophisticated ways to assist the surgeon. Different spatial motion constraints for human machine collaborative systems can be implemented by using this method if we know the required geometric constraints and the instantaneous kinematics of the robot. It is independent of manipulator types: teleoperative or cooperative controlled; admittance or impedance type. Our method uses weighted, linearized, multi-objective optimization framework to formalize a library of virtual fixtures for task primitives. We set the cost function based on the user's inputs, and set linearized subject function based on a combination of five basic geometric constraints. In this paper, we also illustrate the implementation for two sample tasks, which are useful for surgical applications, and provide the experimental results for these tasks.
Identification of Novel HIV‐1 Integrase Inhibitors Using Shape‐Based Screening, QSAR, and Docking Approach (2012)

The objective of this study is to identify novel HIV-1 integrase (IN) inhibitors. Here, shape-based screening and QSAR have been successfully implemented to identify the novel inhibitors for HIV-1 IN, and in silico validation is performed by docking studies. The 2D QSAR model of benzodithiazine derivatives was built using genetic function approximation (GFA) method with good internal (cross-validated r(2) = 0.852) and external prediction (). Best docking pose of highly active molecule of the benzodithiazine derivatives was used as a template for shape-based screening of ZINC database. Toxicity prediction was also performed using Deductive Estimation of Risk from Existing Knowledge (DEREK) program to filter non-toxic molecules. Inhibitory activities of screened non-toxic molecules were predicted using derived QSAR models. Active, non-toxic screened molecules were also docked into the active site of HIV-1 IN using AutoDock and dock program. Some molecules docked similarly as highly active molecule of the benzodithiazine derivatives. These molecules also followed the same docking interactions in both the programs. Finally, four benzodithiazine derivatives were identified as novel HIV-1 integrase inhibitors based on QSAR predictions and docking interactions. ADME properties of these molecules were also computed using Discovery Studio.
A Miniaturized Single-Transducer Implantable Pressure Sensor With Time-Multiplexed Ultrasonic Data and Power Links (2018)

A high-precision implantable pressure sensor with ultrasonic power-up and data uplink is presented. The fully packaged implant measures 1.7 × 2.3 × 7.8 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> and includes a custom IC designed in a 180-nm HV BCD process, a pressure transducer, an energy storage capacitor, and a single piezoelectric transducer (piezo). In order to reduce overall dimensions, unique circuit and system design techniques are presented to enable a single time-multiplexed piezo for both power recovery and data uplink transmission. Implant performance is characterized at significant depths, 12 cm in a tissue phantom, offering a > 13× improvement over state of the art in the depth/volume figure of merit, while demonstrating a robust ultrasonic data uplink with better than 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-5</sup> bit error rate. A transient charging analysis is presented to derive the optimal piezo impedance and charging specifications to maximize overall harvesting efficiency. The IC features a front end with a 10-bit SAR ADC achieving a pressure full-scale range of 800 mmHg with a pressure resolution of 0.78 mmHg, exceeding the requirements for a wide range of in vivo pressure sensing applications. The pressure sampling rate is fully externally controlled, up to 1 ksps, in order to significantly decrease implant energy consumption and to allow for adaptable programming for specific applications.
NET-02: A multi-center, randomised, phase II trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients (pts) with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma (PD-EP-NEC). (2019)

TPS4158 Background: The prognosis for pts with PD-EP-NEC is poor. First-line treatment for advanced disease is etoposide/platinum-based chemotherapy, analogous to that of high grade lung NEC, with no standard second-line treatment, and is an area of unmet need. Methods: This is a multi-centre, randomised, phase II trial of nal-IRI; 80mg/m 2 intravenously (IV) over 90 mins, prior to 5-FU; 2400 mg/m 2 infusion over 46 hrs and folinic acid, Q14 days, or docetaxel; 75mg/m 2 IV over 60 mins, Q21 days, as second-line therapy in pts with progressive PD-EP-NEC (Ki-67 &gt; 20%), with the overall aim of selecting a treatment for continuation to a phase III trial. The standard arm is that used in high-grade lung NEC, of which docetaxel is a second-line therapy option (NCCN guidelines) and combination regimens such as Irinotecan/5-FU are a second-line therapy option currently used without trial evidence for this subset of pts. Pts must have had prior treatment with first-line platinum-based chemotherapy, have documented disease progression and have an ECOG performance status of ≤2. This study plans to recruit 102 pts from 16 UK centres (over 37 mths). Primary endpoint is 6-mth progression-free survival (PFS) rate; trial is designed to have an 80% chance of demonstrating that the one-sided 95% confidence interval of the 6 mth PFS rate excludes 15%, if the true rate is at least 30%, where 30% is the required level of efficacy, and a rate of &lt; 15% would give grounds for rejection. If both treatment arms exceed the required level of efficacy to warrant further evaluation in a phase III trial, treatment with the higher PFS rate at 6 mths will be selected. Secondary endpoints include overall survival, objective response rate, toxicity, quality of life, serum neuron-specific enolase. Exploratory endpoints include quantification of circulating tumour cells (CTCs), circulating tumour deoxyribonucleic acid (ctDNA) and molecular profiling of CTCs, ctDNA and tumour tissue, and generation of CTC-derived xenografts. This trial is open and has enrolled 6 pts at time of submission. Clinical trial information: 10996604.
Interphase cytogenetic analysis detects minimal residual disease in a case of acute lymphoblastic leukemia and resolves the question of origin of relapse after allogeneic bone marrow transplantation (1991)

We used in situ hybridization with a probe for the X chromosome to study interphase cells of bone marrow and peripheral blood specimens from a male patient with acute lymphoblastic leukemia characterized by hyperdiploidy, including trisomy X. In a posttreatment bone marrow specimen, which was interpreted as a regenerating bone marrow morphologically and which demonstrated a normal karyotype cytogenetically, trisomy X was found in 16 of 1,000 interphase cells. This finding indicated the presence of leukemic cells that were undetected by conventional morphologic and cytogenetic techniques (ie, minimal residual disease). Cytogenetic studies of a relapse specimen obtained after a sex-mismatched bone marrow transplant showed only a normal female karyotype in each of 40 metaphase cells, suggesting that the relapse occurred in donor cells. However, interphase analysis demonstrated trisomy X in more than 80% of interphase cells and indicated that the relapse was of the original clone and was not a transformation of donor cells. This case illustrates that interphase analysis can be useful as an adjunct to conventional cytogenetic analysis in the detection of minimal residual disease and in the analysis of interphase cells that are not accessible to routine cytogenetic methods. It also illustrates that previously reported instances of relapse of leukemia in donor cells could have been incorrect if supported by cytogenetic data alone.
Protein Kinase C:  Structural and Spatial Regulation by Phosphorylation, Cofactors, and Macromolecular Interactions (2001)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein Kinase C: Structural and Spatial Regulation by Phosphorylation, Cofactors, and Macromolecular InteractionsAlexandra C. NewtonView Author Information Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0640 Cite this: Chem. Rev. 2001, 101, 8, 2353–2364Publication Date (Web):June 30, 2001Publication History Received17 January 2001Published online30 June 2001Published inissue 1 August 2001https://pubs.acs.org/doi/10.1021/cr0002801https://doi.org/10.1021/cr0002801research-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views4104Altmetric-Citations759LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cell and molecular biology,Lipids,Membranes,Peptides and proteins,Post-translational modification Get e-Alerts
Stabilization of lipid bilayer vesicles by sucrose during freezing (1986)

The freeze-induced fusion and leakage of small unilamellar vesicles (SUV) of natural and synthetic phosphatidylcholines and the suppression of these processes by sucrose was studied by electron microscopy, by high-resolution NMR, and by ESR techniques. During slow freezing of SUV suspensions in water, the lipid was compressed into a small interstitial volume and transformed into a multilamellar aggregate without vesicular structure. When frozen in sucrose solution, the lipid also was compressed between the ice crystals but remained in the form of vesicles. The fractional amount of lipid remaining as SUV after freezing was found to increase significantly only at sucrose/lipid molar ratios above 0.4. Eu(3+) displaced sucrose from the lipid by competitive binding. During freezing in the absence of sucrose, the vesicles became transiently permeable to ions. ESR studies showed that fusion of vesicles in the absence of sucrose is far more extensive when they are frozen while above their phase-transition temperature (t(c)) than when frozen while below their t(c). It is concluded that the extent of membrane disruption depends on the membrane mobility at the moment of freezing and that sucrose exerts its protective effect by binding to the membrane interface and/or by affecting the water structure.
Hollow multilayer photonic bandgap fibers for NIR applications (2004)

Here we report the fabrication of hollow-core cylindrical photonic bandgap fibers with fundamental photonic bandgaps at near-infrared wavelengths, from 0.85 to 2.28 microm. In these fibers the photonic bandgaps are created by an all-solid multilayer composite meso-structure having a photonic crystal lattice period as small as 260 nm, individual layers below 75 nm and as many as 35 periods. These represent, to the best of our knowledge, the smallest period lengths and highest period counts reported to date for hollow PBG fibers. The fibers are drawn from a multilayer preform into extended lengths of fiber. Light is guided in the fibers through a large hollow core that is lined with an interior omnidirectional dielectric mirror. We extend the range of materials that can be used in these fibers to include poly(ether imide) (PEI) in addition to the arsenic triselenide (As(2)Se(3)) glass and poly(ether sulfone) (PES) that have been used previously. Further, we characterize the refractive indices of these materials over a broad wavelength range (0.25 - 15 microm) and incorporated the measured optical properties into calculations of the fiber photonic band structure and a preliminary loss analysis.
Overview of recent direct wafer bonding advances and applications (2011)

Direct wafer bonding processes are being increasingly used to achieve innovative stacking structures. Many of them have already been implemented in industrial applications. This article looks at direct bonding mechanisms, processes developed recently and trends. Homogeneous and heterogeneous bonded structures have been successfully achieved with various materials. Active, insulating or conductive materials have been widely investigated. This article gives an overview of Si and SiO2 direct wafer bonding processes and mechanisms, silicon-on-insulator type bonding, diverse material stacking and the transfer of devices. Direct bonding clearly enables the emergence and development of new applications, such as for microelectronics, microtechnologies, sensors, MEMs, optical devices, biotechnologies and 3D integration.
Modular, Gold-Catalyzed Approach to the Synthesis of Lead-like Piperazine Scaffolds (2013)

Ring-opening of cyclic sulfamidates with propargylic sulfonamides yielded substrates for a gold-catalyzed cyclization to yield tetrahydropyrazines. Manipulation of the tetrahydropyrazines, by reduction or using multicomponent reactions, yielded piperazine scaffolds in which substitution of the carbon atoms was varied. Such scaffolds may have value in the synthesis of novel screening compounds with lead-like molecular properties.
Hpt, a bacterial homolog of the microsomal glucose- 6-phosphate translocase, mediates rapid intracellular proliferation in Listeria (2001)

Efficient replication in vivo is essential for a microparasite to colonize its host and the understanding of the molecular mechanisms by which microbial pathogens grow within host tissues can lead to the discovery of novel therapies to treat infection. Here we present evidence that the foodborne bacterial pathogen Listeria monocytogenes, a facultative intracellular parasite, exploits hexose phosphates (HP) from the host cell as a source of carbon and energy to fuel fast intracellular growth. HP uptake is mediated by Hpt, a bacterial homolog of the mammalian translocase that transports glucose-6-phosphate from the cytosol into the endoplasmic reticulum in the final step of gluconeogenesis and glycogenolysis. Expression of the Hpt permease is tightly controlled by the central virulence regulator PrfA, which upon entry into host cells induces a set of virulence factors required for listerial intracellular parasitism. Loss of Hpt resulted in impaired listerial intracytosolic proliferation and attenuated virulence in mice. Hpt is the first virulence factor to be identified as specifically involved in the replication phase of a facultative intracellular pathogen. It is also a clear example of how adaptation to intracellular parasitism by microbial pathogens involves mimicry of physiological mechanisms of their eukaryotic host cells.
Fecal microbiota transplantation broadening its application beyond intestinal disorders (2015)

Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.
Research report: information animation applications in the capital markets (2002)

3D computer graphics can be extremely expressive. It is possible to display an entire securities market, like the S&P 500, on a single screen. With the correct approach to the visual design of the layout, these massive amounts of information can be quickly and easily comprehended by a human observer. By using motion and animated interaction, it is possible to use 3D as a reliable, accurate and precise decision-support tool. Information animation applications are particularly suited to the securities industry because that is where we find huge amounts of data, the value of which declines rapidly with time, and where critical decisions are being made on this data in very short periods of time. Information animation technology is an important new tool for the securities industry, where people need to be in the decision-making loop without suffering from information overload. Several examples are discussed including equity trading analytics, fixed income trading analytics and fixed-income risk viewing.
Transmission performance of all-optically labelled packets using ASK/DPSK orthogonal modulation (2003)

First transmission experiment with all-optically labelled packets consisting of ASK modulated payload and orthogonally modulated DPSK label is demonstrated. The limitation of the laser linewidth and the input extinction ratio are discussed.
Accelerometer based line-of-sight stabilization approach for pointing and tracking systems (2002)

Equipment operating from nonstationary platforms are subjected to angular jitter resulting from vehicle linear and angular motions. The purpose of a stabilized platform is to reject the angular disturbances so that the device modulation transfer function (MTF) is preserved at the system level. This paper describes a new platform stabilization approach where miniature, low-cost, linear accelerometers are used (instead of gyroscopes) for line-of-Sight (LOS) stabilization. This is accomplished by placing the accelerometers at strategic locations, and combining their outputs so that angular motion is determined from linear acceleration measurements. The control system uses the sensed angular accelerations to generate movement commands for the gimbal servomotors in the stabilization platform. This counter-rotates the imaging device to stabilize its LOS. The use of accelerometers allows the servo system to operate in an acceleration control mode which is more desirable than position or velocity control modes, typical of gyro-based systems, since this increases stabilization bandwidth. Substituting gyros with accelerometers provides the additional benefits of lower sensor cost, weight and power consumption, better temperature characteristics, more robustness, and higher shock resistance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The adaptive multi-rate wideband codec: history and performance (2003)

This paper gives the history and performance of the adaptive multi-rate wideband (AMR-WB) speech codec recently selected by the Third Generation Partnership Project (3GPP) for GSM and the third generation mobile communication WCDMA system for providing wideband speech services. The AMR-WB speech codec algorithm was selected in December 2000, and the corresponding specifications were approved in March 2001. In July 2001, the AMR-WB codec was also selected by ITU-T in the standardization activity for wideband speech coding around 16 kbit/s. The adoption of AMR-WB by ITU-T is of significant importance since for the first time the same codec is adopted for wireless as well as wireline services. AMR-WB uses an extended audio bandwidth from 3.4 kHz to 7 kHz and gives superior speech quality and voice naturalness compared to 2/sup nd/ and 3/sup rd/ generation mobile communication systems.
MMI multiplexer for dual-channel erbium-doped waveguide amplifiers (2001)

A multimode interference coupler is proposed for pumping two erbium-doped waveguide amplifiers from a single 980 nm pump channel. Simulations predict that a device less than 2500 microm long can be made with signal and pump power losses of 0.28 dB and 0.63 dB respectively. The calculated 1 dB excess loss bandwidth of the device is 57 nm.