gebhart/patrepeval huggingface dataset:
Current prices versus minimum costs of production for CFTR modulators (2022)

Abstract Background While the clinical benefits of CFTR modulators are clear, their high prices render them inaccessible outside of a select few countries. Despite this, there is currently limited evidence regarding access to these transformative therapies. Therefore, this study aims to estimate the minimum costs of production of CFTR modulators, assuming robust generic competition, and to compare them with current list prices to evaluate the feasibility of increased global access to treatment. Methods Minimum costs of production for CFTR modulators were estimated via an algorithm validated in previous literature and identification of cost-limiting key starting materials from published routes of chemical synthesis. This algorithm utilised per kilogram active pharmaceutical ingredient costs obtained from global import/export data. Estimated production costs were compared with published list prices in a range of countries. Results Costs of production for tezacaftor/ivacaftor/elexacaftor are estimated at $5676 [$4811-6539] per year, over 90% lower than the US list price. Analysis of chemical structure and published synthetic pathways for tezacaftor/ivacaftor/elexacaftor revealed relatively straightforward routes of synthesis related to currently available products. Total cost of triple therapy for all eligible diagnosed CF patients would be $489 million per year. Comparatively, the annual cost at US list price would be $31.2 billion. Conclusion Tezacaftor/ivacaftor/elexacaftor could be produced via generic companies for a fraction of the list price. The current pricing model restricts access to the best available therapy in LMICs, thereby exacerbating existing international inequalities in CF care. Urgent action is needed to increase availability of triple combination treatment worldwide. Funding None
Advances and trends in ionophore-based chemical sensors (2015)

The recent advances in the theory and practice of potentiometric, conductometric and optical sensors based on ionophores are critically reviewed. The role of the heterogeneity of the sensor/sample systems is emphasized, and it is shown that due to this heterogeneity such sensors respond to the analyte activities rather than to concentrations. The basics of the origin of the response of all three kinds of ionophore-based sensors are briefly described. The use of novel sensor materials, new preparation and application techniques of the sensors as well as advances in theoretical treatment of the sensor response are analyzed using literature sources published mainly from 2012 to 2014. The basic achievements made in the past are also addressed when necessary for better understanding of the trends in the field of ionophore-based sensors. The bibliography includes 295 references.
Incorporating Multi-Year Asset Replacement Time Into Calculation of Asset's Expected Annual Unavailability Due to End-of-Life Failure (2021)

Aging asset management requires careful consideration of end-of-life of any asset. This is particularly serious with aging infrastructure which may require complete replacement of a large asset which has a long lead time. In many current End-of-Life analysis approaches to calculate unavailability, the period of interest is sub-divided into yearly cycles with the assumption that the asset is available at the start of the year. Although this assumption is adequate if the replacement time for the asset occurs within the year, with longer lead times this can create excessively optimistic availabilities. This paper presents an improved probabilistic tool for risk assessment due to End-of-Life failure unavailability which overcomes this deficiency. The End-of-Life methodology proposed in this paper is required when aging assets have long lead times to replacement and so the capital investment decision must be made several years ahead. The method is applied to evaluate the End-of-Life unavailability of Manitoba Hydro Bipole II HVdc converters. The results are corroborated using Monte Carlo simulation. Finally, the risk of End-of-Life is incorporated into an economic cost-benefit analysis corresponding to the presented unavailability evaluation method.
Polyampholytes (2004)

Abstract Polyampholytes are charged polymers with both positively and negatively charged groups. The conformation of these polymers in solutions strongly depends on the distribution of charged monomers along the polymer backbone and their environment. In this review we summarize the current level of understanding of such amphoteric polymers in solutions and their interactions with surfaces and polyelectrolytes. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3513–3538, 2004
PSMA-targeted [18F]DCFPyL PET/CT-avid lesions in a patient with prostate cancer: Clinical decision-making informed by the PSMA-RADS interpretive framework (2019)

We present the case of a man with oligometastatic prostate cancer who underwent a PSMA-targeted 18F-DCFPyL PET/CT scan in order to illustrate how the PSMA-RADS grading sytem can be successfully used to support clinical decision-making and treatment planning. Notably, the presented patient was found to have an equivocal bone lesion (PSMA-RADS-3B) which was further worked up with a tumor protocol MRI and found to be definitively benign (PSMA-RADS-1B) and thus removed from the oligometastatic treatment plan. Remaining avid lesions were incorporated into the treatment plan or deferred for later work-up or monitoring, as indicated within the PSMA-RADS framework.
High-repetition-rate tunable narrowband terahertz-wave generation based on nonlinear frequency conversion pumped by dual fiber lasers in MgO:LiNbO3 (2018)

We demonstrate a high-average-power, single-longitudinal-mode, and tunable terahertz-wave (THz-wave) source based on difference frequency generation (DFG) in a MgO:LiNbO<sub>3</sub> (MgO:LN) crystal. The DFG waves are generated using a pair of Yb-doped, pulsed fiber lasers with a master oscillator power fiber amplifier configuration. The average power of the THz-wave output reaches 1.35 mW at 1.0 THz (300 &mu;m) at a linewidth of 7.2 GHz, and the tunability ranges from 0.34 to 1.25 THz under a pulse repetition frequency of 500 kHz. With this scheme, we constructed a compact THz-wave generation head for imaging applications. The combination of MgO:LN-DFG and the stable and robust fiber laser sources is highly promising for developing high-average-power THz-wave sources, particularly in the high-transmission sub-THz region. This approach may enable new applications of THz-wave spectroscopy in imaging and remote sensing.
Osmium imido complexes: synthesis, reactivity, and SCF-X.alpha.-SW electronic structure (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOsmium imido complexes: synthesis, reactivity, and SCF-X.alpha.-SW electronic structureMark H. Schofield, Terence P. Kee, Jens T. Anhaus, Richard R. Schrock, Keith H. Johnson, and William M. DavisCite this: Inorg. Chem. 1991, 30, 19, 3595–3604Publication Date (Print):September 18, 1991Publication History Published online1 May 2002Published inissue 18 September 1991https://pubs.acs.org/doi/10.1021/ic00019a006https://doi.org/10.1021/ic00019a006research-articleACS PublicationsRequest reuse permissionsArticle Views364Altmetric-Citations93LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
maT—A Clade of Transposons Intermediate Between mariner and Tc1 (2002)

A group of transposons, named maT, with characteristics intermediate between mariner and Tc1 transposons, is described. Two defective genomic copies of MdmaT from the housefly Musca domestica, with 85% identity, were found flanking and imbedded in the MdalphaE7 esterase gene involved in organophosphate insecticide resistance. Two cDNA clones, with 99% identity to each other and 72%-89% identity to the genomic copies were also obtained, but both represented truncated versions of the putative open reading frame. A third incomplete genomic copy of MdmaT was also identified upstream of the putative M. domestica period gene. The MdmaT sequences showed high identity to the transposable element Bmmar1 from the silkworm moth, Bombyx mori, and to previously unidentified sequences in the genome of Caenorhabditis elegans. A total of 16 copies of full-length maT sequences were identified in the C. elegans genome, representing three variants of the transposon, with 34%-100% identity amongst them. Twelve of the copies, named CemaT1, were virtually identical, with eight of them encoding a putative full length, intact transposase. Secondary structure predictions and phylogenetic analyses confirm that maT elements belong to the mariner-Tc1 superfamily of transposons, but their intermediate sequence and predicted structural characteristics suggest that they belong to a unique clade, distinct from either mariner-like or Tc1-like elements.
Toward a Combined Molecular Dynamics and Quantum Mechanical Approach to Understanding Solvent Effects on Chemical Processes in the Pharmaceutical Industry: The Case of a Lewis Acid-Mediated SNAr Reaction (2023)

Solvation effects on chemical reactions can have a significant impact on the development of chemical processes in the pharmaceutical industry. Evaluating solvation effects at the atomic level would provide greater insight and understanding into their impact on chemical transformations. However, modeling complex reaction systems at this level of detail is challenging and a consistent approach of evaluation has not been established. Herein, we describe our initial results on the development of a practical solvation modeling protocol, which combines classical/ab initio molecular dynamics and density functional theory-based techniques with trajectory clustering, identification of solvent shells, and subsequent wave function analysis for characterizing a range of diverse interactions in the multicomponent solvation system. We describe how our solvation modeling protocol attempts to capture and describe these interactions objectively and simultaneously in the drug substance-forming step for the manufacture of 3, an SNAr reaction of aryl chloride 1 and pyrrolidine 2.
Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells (2016)

Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retro- or lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro- or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation.
Household Members Do Not Contact Each Other at Random: Implications for Infectious Disease Modelling (2017)

Airborne infectious diseases such as influenza are primarily transmitted from human to human by means of social contacts and thus easily spread within households. Epidemic models, used to gain insight in infectious disease spread and control, typically rely on the assumption of random mixing within households. Until now there was no direct empirical evidence to support this assumption. Here, we present the first social contact survey specifically designed to study contact networks within households. The survey was conducted in Belgium (Flanders and Brussels) in 2010-2011. We analyzed data from 318 households totaling 1266 individuals with household sizes ranging from 2 to 7 members. Exponential-family random graph models (ERGMs) were fitted to the within-household contact networks to reveal the processes driving contact between household members, both on weekdays and weekends. The ERGMs showed a high degree of clustering and, specifically on weekdays, decreasing connectedness with increasing household size. Furthermore, we found that the odds of a contact between father and child is smaller than for any other pair except for older siblings. Epidemic simulation results suggest that within-household contact density is the main driver of differences in epidemic spread between complete and empirical-based household contact networks. The homogeneous mixing assumption may therefore be an adequate characterization of the within-household contact structure for the purpose of epidemic simulation. However, ignoring the contact density when inferring from an epidemic model will result in biased estimates of within-household transmission rates. Further research on the implementation of within-household contact networks in epidemic models is necessary. Significance Statement Households have a pivotal role in the spread of airborne infectious diseases. Households are bridging units between schools and workplaces, and social contacts within households are frequent and intimate, allowing for rapid disease spread. Infectious disease models typically assume that members of a household contact each other randomly. Until now there was no direct empirical evidence to support this assumption. In this paper, we present the first social contact survey specifically designed to study contact networks within households with young children. We investigate which factors drive contacts between household members on one particular day by means of a statistical model. Our results suggest the importance of connectedness within households over heterogeneity in number of contacts.
Post-translational regulation of IgM expression in B lymphocytes. Selective nonlysosomal degradation of assembled secretory IgM is temperature-dependent and occurs prior to the trans-Golgi (1991)

B cells express on their surface the membrane form of IgM (mIgM). Upon differentiation, the resulting plasma cells synthesize and secrete large amounts of the secretory form of IgM (sIgM). Surprisingly, B lymphocytes synthesize an excess of secretory mu chain over the expressed membrane mu chain. However, the sIgM is degraded intracellularly, indicating regulation of IgM expression at the post-translational level. In the present report, we show that the assembly, maturation, and degradation of IgM in 38C B lymphocytes are highly accelerated above a certain threshold temperature. Furthermore, the degradation of sIgM is delayed and takes place by the time the maturation of mIgM in the trans-Golgi is almost completed. Neither chloroquine nor monensin has any effect on this degradation, demonstrating a nonlysosomal pre-trans-Golgi process. In addition, the degradation is of endoglycosidase H-sensitive assembled sIgM molecules. We conclude that the degradation of sIgM in 38C B lymphocytes is a postendoplasmic reticulum, pre-trans-Golgi process. We suggest that this degradation process plays a role in the post-translational regulation of expression of soluble lumenal sIgM.
Measurements of the Varus Knee and Their Influence on Implant Design (2018)

Introduction:Varus alignment of the knee is common in patients undergoing unicondylar knee replacement. To measure the geometry and morphology of these knees is to know whether a single unicondylar...
Lateral stiffness of the tip and tip-sample contact in frictional force microscopy (1997)

In atomic force and frictional force microscopy, quantitative interpretation of lateral stiffness at the tip-sample contact requires a detailed understanding of all factors contributing to the frictional force as measured in a typical experiment. We used a scanning transmission electron microscope to image and determine the geometry of the tip apex of a variety of atomic force microscope cantilevers. On the basis of this measured structure, we then used finite element analysis to model the lateral stiffness of the tip and found that the tip stiffness is often smaller than the lateral stiffness of the cantilever. Furthermore, we analyzed the stiffness of the tip sample contact and found that for sharp tips the contact stiffness can also be comparable to the lateral stiffness of the cantilever. If these two effects are ignored, significant errors can result in the calculation of lateral forces. We demonstrated the effects of lateral tip and contact stiffness experimentally and used the measurements to calculate the radius of the tip-sample contact.
The Design of LED Fiber Automotive Headlamp (2016)

It's more and more common to use LED as the light source in automotive lighting. But heat dissipation and low light output of single die light source have restricted the LED to be the mainstream. To use fiber as light-transmitting component could perfectly resolve above weakness. In the paper a design method of LED fiber automotive headlamp is mentioned. And for COB (chip on board) LED, a mathematic model of TIR (total internal reflected) lens is proposed. It could effectively focus the rays emitted from surface light source.
RTDS Based Maximal Power Point Tracking Simulation for Doubly-Fed Induction Generator (2009)

In the control of the wind generation, the maximal power point tracking (MPPT) control plays important role in the efficiency. This paper presents the simulation results of the MPPT control with RTDS-based DFIG model. At first, it analyzes the vector-control scheme for the MTTP, which results in independent control of active and reactive power of the generator. And then, it develops the MPPT controller implemented on the rectifier and inverter based on PI control strategic. Furthermore, it builds the DFIG model based on the RTDS with the corresponding technology. And the simulation result with the proposed model verified the control strategy.
Asymmetric Synthesis of (S)‐2‐Indolinecarboxylic Acid by Combining Biocatalysis and Homogeneous Catalysis (2011)

A tale of two catalysts: (S)-2-Indolinecarboxylic acid, an intermediate for ACE inhibitors, was until recently produced by Fischer indole synthesis and classical resolution in seven steps. However, Perkin condensation to form ortho-chlorocinnamic acid, which is converted to (S)-ortho-chlorophenylalanine using the enzyme phenylalanine ammonia lyase prior to copper-catalyzed ring closure thereof delivers the enantiopure product in just three steps.
Surfactant-Controlled Size and Shape Evolution of Magnetic Nanoparticles (2008)

This manuscript describes a simple one-pot reaction that affords cuboid iron−manganese oxide nanoparticles with unprecedented dimensions as large as 33 ± 5 nm (average body-centered diagonal) in monodisperse form. Our unique synthetic method, which requires no multiple growth steps typical of other methods, utilizes the thermal decomposition of metal precursor complexes in the presence of specifically tailored surfactants and/or mixtures of surfactants. The size and shape of these unusually large magnetic nanoparticles (MNPs) can be manipulated at will simply by adjusting the surfactant composition, leading to enhanced control over the dimensions of the nanoparticles because of the surface-differentiating influence of the functional end groups. Our surfactant system utilizes two types of surface ligands: one strongly bound to the metal surface and the others loosely bound. This combination of ligands plays an important role in controlling particle size and morphology. With an eye toward potential biomedical applications, the magnetic properties of the MNPs were investigated through their M−H hysteresis loop behavior at 290 K. More importantly, when exposed to a magnetic field, relaxation measurements of these MNPs afforded Néel relaxation times of 3.4 s at an average body-centered diagonal size of 29 ± 4 nm.
Distribution of the figures 0 and 1 in the various orders of binary representations of 𝑘𝑡ℎ powers of integers (1968)

of the periodic repetition of the figures 0 and 1 in the columns of tables formed by writing successively the binary representations of the values taken by polynomials in x of arbitrary degree when x is given all the values of the positive integers, prompted R. Vacca to carry out counts of the figures 0 and 1 in the columns of tables formed by the fcth powers of integers (with k an integer), which he did by means of appropriate programs for the FINAC electronic computer at Istituto Nazionale per le Applicazioni del Calclo in Rome. Obviously in the order 2 the number of figures equal to 1 is equal to the number of figures equal to 0 for any k. It was also observed that for h > 0 the number of figures equal to 1 in the order 2A is less than or equal to the number of figures equal to 0, that for increasing values of h the ratio between the number of figures equal to 1 and the total number of figures within a periodic sequence tends to the value and that the value is reached periodically, in the table of fcth powers, every k orders, or in all columns 2h for which h is divisible by fc and for fc > 2.
Mapping Charge Recombination and the Effect of Point Defect Insertion in Gallium Arsenide Nanowire Heterojunctions (2020)

Electronic devices are extremely sensitive to defects in their constituent semiconductors, but locating electronic point defects in bulk semiconductors has previously been impossible. Here we apply scanning transmission electron microscopy (STEM) electron beam-induced current (EBIC) imaging to map electronic defects in a GaAs nanowire Schottky diode. Imaging with a non-damaging 80 or 200 kV STEM acceleration potential reveals a minority-carrier diffusion length that decreases near the surface of the hexagonal nanowire, thereby demonstrating that the device's charge collection efficiency (CCE) is limited by surface defects. Imaging with a 300 keV STEM beam introduces vacancy-interstitial (VI, or Frenkel) defects in the GaAs that increase carrier recombination and reduce the CCE of the diode. We create, locate, and characterize a single insertion event, determining that a defect inserted 7 nm from the Schottky interface broadly reduces the CCE by 10% across the entire nanowire device. Variable-energy STEM EBIC imaging thus allows both benign mapping and pinpoint modification of a device's e-h recombination landscape, enabling controlled experiments that illuminate the impact of both extended (1D and 2D) and point (0D) defects on semiconductor device performance.