gebhart/patrepeval huggingface dataset:
Leveraging subject-specific musculoskeletal modeling to assess effect of anterior cruciate ligament retaining total knee arthroplasty during walking gait (2020)

Bi-cruciate retaining total knee arthroplasty has several potential advantages including improved anteroposterior knee stability compared to contemporary posterior cruciate-retaining total knee arthroplasty. However, few studies have explored whether there is significant differences of knee biomechanics following bi-cruciate retaining total knee arthroplasty compared to posterior cruciate-retaining total knee arthroplasty. In the present study, subject-specific lower extremity musculoskeletal multi-body dynamics models for bi-cruciate retaining, bi-cruciate retaining without anterior cruciate ligament, and posterior cruciate-retaining total knee arthroplasty were developed based on the musculoskeletal modeling framework using force-dependent kinematics method and validated against in vivo telemetric data. The experiment data of two subjects who underwent total knee arthroplasty were obtained for the SimTK "Grand Challenge Competition" repository, and integrated into the musculoskeletal model. Five walking gait trials for each subject were used as partial inputs for the model to predict the knee biomechanics for bi-cruciate retaining, bi-cruciate retaining without anterior cruciate ligament, and posterior cruciate-retaining total knee arthroplasty. The results revealed significantly greater range of anterior/posterior tibiofemoral translation, and significantly more posterior tibial location during the early phase of gait and more anterior tibial location during the late phase of gait were found in bi-cruciate retaining total knee arthroplasty without anterior cruciate ligament when compared to the bi-cruciate retaining total knee arthroplasty. No significant differences in tibiofemoral contact forces, rotations, translations, and ligament forces between bi-cruciate retaining and posterior cruciate-retaining total knee arthroplasty during normal walking gait, albeit slight differences in range of tibiofemoral internal/external rotation and anterior/posterior translation were observed. The present study revealed that anterior cruciate ligament retention has a positive effect on restoring normal knee kinematics in bi-cruciate retaining total knee arthroplasty. Preservation of anterior cruciate ligament in total knee arthroplasty and knee implant designs interplay each other and both contribute to restoring normal knee kinematics in different types of total knee arthroplasty. Further evaluation of more demanding activities and subject data from patients with bi-cruciate retaining and posterior cruciate-retaining total knee arthroplasty via musculoskeletal modeling may better highlight the role of the anterior cruciate ligament and its stabilizing influence.
Numerically study the method to tune the intensity of the surface plasmon (2005)

There are two modes of surface plasmon, radiative and nonradiative. Theoretically, the evanescent surface electric fileds (nonradiative surface plasmon) have their maximum on the surface and exponentially decaying field perpendicular to it. Though the evanescent surface wave can not radiate, the enhancement of the surface electric field has become an important feature in plasmonics. Especially, if one can control the enhancement factor of a plasmonic device, that is, if the intensity of the optical near field which is excited on a plasmonic object can be adjusted exactly, there will be many novel applications implemented. Based on three-dimensional finite-difference time-domain method, we analyze the interactions of the two identical spherical silver particles with optical wave. Our results show that the electric amplitudes at the midpoint of the two particles are dependent on the direction of the alignment. We convince that by changing the angle between the alignment of the particles and the polarization, the local electric intensity would be tuned well.
Rate-equation model of light-induced heating in LiNbO_3-type crystals under high-average-power laser irradiation (2016)

Light-induced heating under high-average-power laser is investigated in LiNbO3-type crystals in green second-harmonic generation. A rate-equation based on the kinetics of polarons is proposed and important parameters of the rate-equation are determined by reproducing experimental results. Light-induced heat and threshold intensity of catastrophic breakdown are evaluated using the rate-equation. The accumulation effect of polarons causes the decrease of threshold intensity of catastrophic breakdown of crystals.
Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining theH→γγandH→ZZ*→4ℓDecay Channels ats=8  TeVwith the ATLAS Detector (2015)

Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb^{-1} of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of sqrt[s]=8 TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ^{*}→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σ_{pp→H}=33.0±5.3 (stat)±1.6 (syst) pb. The measurements are compared to state-of-the-art predictions.
Improved Precision Time Protocol with Relative Clock Phase Information (2018)

The following topics are dealt with: synchronisation; protocols; clocks; IEEE standards; cryptographic protocols; telecommunication traffic; public key cryptography; computer network security; telecommunication security; field programmable gate arrays.
High Noise Margin, Digital Logic Design Using Josephson Junction Field-Effect Transistors for Cryogenic Computing (2021)

As compute demands and their large energy costs continue to rise in the datacenter, it is imperative to identify low energy compute solutions. One approach is to investigate device schemes based on collective mode phenomena arising at low temperatures where power dissipation and switching voltage can be extremely low. Additionally, such devices could also have applications in quantum computing where such a low power logic/memory scheme could possibly be integrated onto the qubit plane, which is typically at ~10 mK temperature. Josephson Junction Field Effect Transistor (JJFET) is a promising candidate for low power operation with zero voltage drop across its drain-source terminals while operating in the superconducting regime. JJFET logic gate is typically realized as a n-type JJFET connected in a common-source configuration with a current source load. This results in high noise margin for logic-1 input but not for both logic-1 and 0. In this paper, we propose an overdamped region, n-type JJFET based digital logic using a cascaded common-source configuration-based design yielding high noise margin for both the logic inputs. DC noise margin sensitivity analysis is performed for the bias current and threshold voltage modulation. The noise margin can be further improved (approaches ideal inverter case) by cascading multiple common source stages yielding higher inverter gain.
Protein design as a challenge for peptide chemists (1995)

All efforts to turn the ultimate goal in protein de novo design into reality-the construction of new macromolecules with predetermined three-dimensional structure and well-defined functionality-failed because the mechanism of folding has still to be unravelled. In the present review, various attempts to apply synthetic tools for inducing native-like structural features in peptides in order to bypass the folding problem are described. Besides well-established methods for the nucleation and stabilization of secondary structures, e.g. alpha-helices, beta-sheets and beta-turns, topological templates as 'built-in' folding devices have more recently become the key elements for the induction of protein-like folding units (template-assembled synthetic proteins, TASP). Progress in the synthetic strategy and structural characterization of this new type of macromolecules opens the way for the design of functional TASP molecules.
Low molecular weight (LMW) orally bioavailable inhibitors of tumor vascular endothelial growth factor (VEGF) translation delay tumor growth in vivo: A new approach to inhibition of angiogenesis (2004)

3123 Background: VEGF plays a critical role in the pathogenic angiogenesis associated with a number of diseases including cancer. Blockade of VEGF by a humanized monoclonal antibody or by inhibitors of the KDR VEGF receptor slows tumor growth in preclinical and clinical studies. However, antibodies must be injected and may have stochiometric limitations in the context of high local concentrations of VEGF at the tumor site. KDR inhibitors will not block flk-receptor mediated responses. Here, we (1) evaluate the pharmacokinetic properties of a series of orally administered LMW compounds that target the untranslated regions (UTRs) of the VEGF mRNA and inhibit its translation and (2) demonstrate the efficacy of these compounds in vivo. Methods: Human fibrosarcoma tumors were established in nude mice. Once tumors were 100 mm3, mice were treated with LMW UTR-specific inhibitors of VEGF translation or with vehicle by oral gavage. At the end of the study, tumors and plasma were collected. Drug concentrations were measured using LC-MS/MS. Intra-tumor human VEGF, human survivin, and human FGF-2 were measured using specific ELISA assays. Results: These compounds effectively inhibited tumor growth. A dose of 50 mg/kg of one of the more potent compounds extended the time for the tumor to reach 1 cm3 to 56 days, compared to 21 days with vehicle. These compounds inhibited intra-tumor VEGF production, but did not inhibit intra-tumor survivin or bFGF levels. Efficacy in these studies correlated with trough plasma drug levels at the end of the study that were at least 5-fold above the in vitro EC90 value. Conclusions: Orally bioavailable LMW compounds can specifically and potently inhibit translation of tumor VEFG, resulting in significant tumor growth delay. Pharmacodynamic efficacy correlates with drug exposure in vivo, suggesting the need for continuous inhibition of VEGF production for efficacy. Efficacy in vivo also correlates with the in vitro EC90 as opposed to the EC50, suggesting that VEGF production must be significantly inhibited to delay tumor growth. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PTC Therapeutics
The Pharmaceutical Development of Insulin: Historical Perspectives and Future Directions (1997)

The pharmaceutical development of insulin has revolutionized diabetes therapy since it was introduced and clinically validated in the 1920's. Due to its importance for therapeutic use in a large and expanding market, insulin has been the focus of intense research in both academia and industry. As a result, there is currently much information available on the physical, chemical and biological aspects of insulin activity. Over the course of the clinical advancement of insulin, there has been a corresponding development in other areas related to biopharmaceutics, e.g., in federal regulation of biological drugs. Insulin formulations have advanced since the early days of crude pancreatic extracts to complex biphasic mixtures involving highly purified preparations of genetically engineered recombinant human protein. Insulin still remains a model for the biopharmaceutical industry. Current research in insulin therapy for diabetes is aimed at improving the insulin molecule and its formulations, developing novel methodologies for its delivery, and further understanding its stability.
SEPSIS-INDUCED INTESTINAL MICROVASCULAR AND INFLAMMATORY RESPONSES IN OBESE MICE (2009)

Although clinical obesity is associated with increases in the morbidity and mortality of sepsis, little is known about the mechanisms that underlie the influence of obesity on sepsis. The objective of this study was to determine (a) whether obesity is associated with exaggerated inflammatory and thrombogenic responses in the intestinal microvasculature of septic mice and (b) whether these microvascular alterations are related to changes in the serum levels of cytokines that are produced by adipose tissue. Intravital microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules of lean wild-type (WT) mice, and two murine models of obesity, that is, ob/ob and db/db mice. Sepsis was induced by cecal ligation and perforation (CLP). Serum cytokine levels were measured using a cytometric bead assay, whereas adipokines were quantified using enzyme-linked immunosorbent assay. Cecal ligation and perforation elicited significant increases in the adhesion of leukocytes and platelets in venules of lean WT mice. These CLP-induced adhesive interactions were much more pronounced in the microvasculature of both ob/ob and db/db mice. Cecal ligation and perforation was associated with significant increases in serum cytokines in both WT and ob/ob mice, but such changes were not detected in db/db mice. However, db/db (but not WT or ob/ob) mice did exhibit significant increases in serum leptin and adiponectin levels after CLP. Sepsis promotes more intense inflammatory and thrombogenic responses in the gut microcirculation of obese mice than in their lean counterparts. The obesity-enhanced microvascular dysfunction in septic mice shows no consistent correlation with serum cytokines or adipokines.
Stable and Storable N(CF3)2 Transfer Reagents (2021)

Fluorinated groups are essential for drug design, agrochemicals, and materials science. The bis(trifluoromethyl)amino group is an example of a stable group that has a high potential. While the number of molecules containing perfluoroalkyl, perfluoroalkoxy, and other fluorinated groups is steadily increasing, examples with the N(CF<sub>3</sub> )<sub>2</sub> group are rare. One reason is that transfer reagents are scarce and metal-based storable reagents are unknown. Herein, a set of Cu<sup>I</sup> and Ag<sup>I</sup> bis(trifluoromethyl)amido complexes stabilized by N- and P-donor ligands with unprecedented stability are presented. The complexes are stable solids that can even be manipulated in air for a short time. They are bis(trifluoromethyl)amination reagents as shown by nucleophilic substitution and Sandmeyer reactions. In addition to a series of benzylbis(trifluoromethyl)amines, 2-bis(trifluoromethyl)amino acetate was obtained, which, upon hydrolysis, gives the fluorinated amino acid N,N-bis(trifluoromethyl)glycine.
Functional and shunt states of bacteriorhodopsin resolved by 250 GHz dynamic nuclear polarization–enhanced solid-state NMR (2009)

Observation and structural studies of reaction intermediates of proteins are challenging because of the mixtures of states usually present at low concentrations. Here, we use a 250 GHz gyrotron (cyclotron resonance maser) and cryogenic temperatures to perform high-frequency dynamic nuclear polarization (DNP) NMR experiments that enhance sensitivity in magic-angle spinning NMR spectra of cryo-trapped photocycle intermediates of bacteriorhodopsin (bR) by a factor of approximately 90. Multidimensional spectroscopy of U-(13)C,(15)N-labeled samples resolved coexisting states and allowed chemical shift assignments in the retinylidene chromophore for several intermediates not observed previously. The correlation spectra reveal unexpected heterogeneity in dark-adapted bR, distortion in the K state, and, most importantly, 4 discrete L substates. Thermal relaxation of the mixture of L's showed that 3 of these substates revert to bR(568) and that only the 1 substate with both the strongest counterion and a fully relaxed 13-cis bond is functional. These definitive observations of functional and shunt states in the bR photocycle provide a preview of the mechanistic insights that will be accessible in membrane proteins via sensitivity-enhanced DNP NMR. These observations would have not been possible absent the signal enhancement available from DNP.
Custom design of a VLSI PCM-FDM transmultiplexer from system specifications to circuit layout using a computer-aided design system (1986)

The computer-aided design of a VLSI PCM-FDM transmultiplexer is presented. The entire design process, from system specifications to integrated circuit layout, is carried out with the aid of specialized computer programs for the analysis, synthesis, and optimization at each design level: the filter network, the architecture, and the circuit layout. These CAD tools support a top-down custom design methodology based on bit-serial architectures and standard cells. A customized architecture is constructed which is integrated using a 5-/spl mu/m CMOS cell library. The results are compared with a fully manual design and demonstrate the power of architecture based computer-aided design methodologies for VLSI filtering. By combining both synthesis and optimization aids at each design level it is possible to achieve a high degree of automation while retaining an efficient use of silicon area, high throughput, and moderate power consumption.
Spectral Shaping for Mitigating Backreflections in a Bidirectional 10 Gbit/s Coherent WDM-PON (2013)

Receiver sensitivity penalty due to backreflections in a 10 Gbit/s bidirectional coherent WDM-PON is evaluated for 3 GBd PDM-QPSK. Pulse shaping is applied to reduce the impact of backreflections and enable tolerance to reflections up to -20 dBm.
Multielement Polychromatic 2D Liquid Crystal Dammann Gratings (2022)

Abstract Multielement and multiwavelength switchable Dammann gratings are demonstrated in polymerizable nematic liquid crystal (LC) devices fabricated using two‐photon polymerization direct laser writing. To begin with, a single element 2D Dammann grating, with a diffraction efficiency of around 60%, is fabricated in a thin polymerizable LC layer such that the grating could be activated and deactivated with the application and removal of an external applied voltage. The impact of the fabrication parameters on the resulting intensity distribution in the far‐field diffraction pattern is presented and discussed, along with results for the response times, which are found to be less than that recorded for the regions of the LC device that did not consist of the laser‐written grating. A multielement device is then presented that exhibits two different Dammann gratings that are activated by the application of two different voltage amplitudes. Results for the corresponding far‐field intensity profiles and response times are presented, which demonstrate that high quality laser written switchable Dammann gratings can be fabricated in polymerizable LCs. These switchable elements have potential in programmable beam shaping, microscopy and optical communication devices.
Bringing plant-based veterinary vaccines to market: Managing regulatory and commercial hurdles (2015)

The production of recombinant vaccines in plants may help to reduce the burden of veterinary diseases, which cause major economic losses and in some cases can affect human health. While there is abundant research in this area, a knowledge gap exists between the ability to create and evaluate plant-based products in the laboratory, and the ability to take these products on a path to commercialization. The current report, arising from a workshop sponsored by an Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme, addresses this gap by providing guidance in planning for the commercialization of plant-made vaccines for animal use. It includes relevant information on developing business plans, assessing market opportunities, manufacturing scale-up, financing, protecting and using intellectual property, and regulatory approval with a focus on Canadian regulations.
Scalable Architecture for Service Function Chain Orchestration (2015)

Network Function Virtualization (NFV) enables to implement network functions in software, high-speed packet processing functions which traditionally are dominated by hardware implementations. Virtualized Network Functions (NFs) may be deployed on generic-purpose servers, e.g., in datacenters. The latter enables flexibility and scalability which previously were only possible for web services deployed on cloud platforms. The merit of NFV is challenged by control challenges related to the selection of NF implementations, discovery and reservation of sufficient network and server resources, and interconnecting both in a way which ful fills SLAs related to reliability and scalability. This paper details the role of a scalable orchestrator in charge of finding and reserving adequate resources. The latter will steer network and cloud control and management platforms to actually reserve and deploy requested services. We highlight the role of involved interfaces, propose elements of algorithmic components, and will identify major blocks in orchestration time in a proof of concept prototype which accounts for most functional parts in the considered architecture. Based on these evaluations, we propose several architectural enhancements in order to implement a highly scalable network orchestrator for carrier and cloud networks.
Induction of the DNA damage response by IAP inhibition triggers natural immunity via upregulation of NKG2D ligands in Hodgkin lymphoma in vitro (2013)

Evasion of apoptosis is a hallmark of cancer cells. Inhibitor of apoptosis proteins (IAPs) act as endogenous inhibitors of programmed cell death and are overexpressed in several tumors including Hodgkin lymphoma (HL). Preclinical studies indicate antitumor activity of IAP antagonists and clinical studies in hematological malignancies are underway. Here, we investigate the impact of the small molecule IAP antagonist LCL161 on HL cell lines. Although the antagonist caused rapid degradation of cIAP1 leading to TNFα secretion, LCL161 did not promote apoptosis significantly. However, LCL161 induced expression of MICA and MICB, ligands for the activating immune receptor NKG2D, and enhanced the susceptibility of HL cells to NKG2D-dependent lysis by NK cells. MICA/B upregulation was dependent on activation of the DNA damage response upon LCL161 treatment. Taken together, we demonstrate a novel link between IAP inhibition, DNA damage and immune recognition.
Iterated Local Optimization for Minimum Energy Broadcast (2005)

In our prior work, we presented a highly effective local search based heuristic algorithm called the largest expanding sweep search (LESS) to solve the minimum energy broadcast (MEB) problem over wireless ad hoc or sensor networks. In this paper, the performance is further strengthened by using iterated local optimization (ILO) techniques at the cost of additional computational complexity. To the best of our knowledge, this implementation constitutes currently the best performing algorithm among the known heuristics for MEB. We support this claim through extensive simulation study, comparing with globally optimal solutions obtained by an integer programming (IP) solver. For small network size up to 20 nodes, which is imposed by practical limitation of the IP solver, the ILO based algorithm produces globally optimal solutions with very high frequency (70%), and average performance is within 1.12% of the optimal solution.