gebhart/patrepeval huggingface dataset:
Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products (2020)

Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimination (ADME) features to be chemically stable, to be selective towards the particular site in the body, and to have appropriate safety. Traditional prodrug approach aims to improve physicochemical/biopharmaceutical drug properties; modern prodrugs also include cellular and molecular parameters to accomplish desired drug effect and site-specificity. Here, we present recently investigated prodrugs, their pharmaceutical and clinical advantages, and challenges facing the overall prodrug development. Given examples illustrate that prodrugs can accomplish appropriate solubility, increase permeability, provide site-specific targeting (i.e., to organs, tissues, enzymes, or transporters), overcome rapid drug metabolism, decrease toxicity, or provide better patient compliance, all with the aim to provide optimal drug therapy and outcome. Overall, the prodrug approach is a powerful tool to decrease the time/costs of developing new drug entities and improve overall drug therapy.
Ultra-stable and versatile widefield cryo-fluorescence microscope for single-molecule localization with sub-nanometer accuracy (2015)

We developed a stand-alone cryostat with optical access to the sample which can be adapted to any epi-fluorescence microscope for single-molecule fluorescence spectroscopy and imaging. The cryostat cools the sample to a cryogenic temperature of 89 K, and allows for imaging single molecules using an air objective with a numerical aperture of 0.7. An important property of this system is its excellent thermal and mechanical stability, enabling long-time observations of samples over several hours with negligible drift. Using this system, we performed photo-bleaching studies of Atto647N dye molecules, and find an improvement of the photostability of these molecules by more than two orders of magnitude. The resulting increased photon numbers of several millions allow for single-molecule localization accuracy of sub-nanometer.
The performance of TCM 16-QAM with equalization, diversity and slow frequency hopping for wideband mobile communications (2002)

The use of high level trellis-coded modulation such as TCM 16-QAM, with equalization, diversity, interleaving and slow frequency hopping is investigated for wideband mobile communications. The symbol error rate (SER) performance of those systems in presence of intersymbol interference (ISI) and Rayleigh fading is evaluated by theoretical analysis and computer simulation. Several schemes of combining equalizers with diversity are evaluated by computer simulations. It shows that by choosing a proper interleaving size, number of the frequency hopping and the combining scheme of equalization and space diversity, the proposed system gives considerable performance improvement and can cope with the frequency selective multipath fading in wideband mobile communication systems.
Expression of the<i>Pasteurella multocida ompH</i>gene is negatively regulated by the Fur protein (2001)

The fur gene of Pasteurella multocida has been cloned by complementation of an Escherichia coli fur mutant. The P. multocida fur gene, which encodes a predicted protein of 147 amino acids, displaying the highest identity (89%) with the same protein of Haemophilus influenzae, is negatively regulated by its own product. By construction of a P. multocida fur mutant, it has been demonstrated that the ompH gene, encoding a major structural protein of the outer membrane, presenting high antigenicity power, is negatively regulated by iron and glucose. Furthermore, wild-type and fur-defective cells of P. multocida show the same level of virulence.
Fair Allocation of Scarce Medical Resources in the Time of Covid-19 (2020)

Covid-19 is officially a pandemic. It is a novel infection with serious clinical manifestations, including death, and it has reached at least 124 countries and territories. Although the ultimate course and impact of Covid-19 are uncertain, it is not merely possible but likely that the disease will produce enough severe illness to overwhelm health care infrastructure. Emerging viral pandemics “can place extraordinary and sustained demands on public health and health systems and on providers of essential community services.” Such demands will create the need to ration medical equipment and interventions. Rationing is already here. In the United States, perhaps the earliest example was the near-immediate recognition that there were not enough high-filtration N-95 masks for health care workers, prompting contingency guidance on how to reuse masks designed for single use. Physicians in Italy have proposed directing crucial resources such as intensive care beds and ventilators to patients who can benefit most from treatment. Daegu, South Korea — home to most of that country’s Covid-19 cases — faced a hospital bed shortage, with some patients dying at home while awaiting admission. In the United Kingdom, protective gear requirements for health workers have been downgraded, causing condemnation among providers. The rapidly growing imbalance between supply and demand for medical resources in many countries presents an inherently normative question: How can medical resources be allocated fairly during a Covid-19 pandemic?
Association of Cecal Spirochetes with Pasty Vents and Dirty Eggshells in Layers (1992)

Feces-stained eggshells, diarrhea, and typhlitis were identified in two commercial laying flocks in Ohio. Hens with diarrhea had spirochetes in cecal lumina and crypts. On culture, the spirochetes were motile and non-hemolytic, did not produce indole, had 12 to 15 axial filaments, were 9.2 to 11.7 microns in length and 240 to 370 nm in diameter, and had a wavelength of 5.1 to 6.5 microns on transmission electron microscopy.
<title>High-speed optical feeder-link system using adaptive optics</title> (1997)

We propose a satellite laser communication system between a ground station and a geostationary satellite, named high- speed optical feeder link system. It is based on the application of (a) high-speed optical devices, which have been developed for ground-based high-speed fiber-optic communications, and (b) the adaptive optics which compensates wavefront distortions due to atmospheric turbulences using a real time feedback control. A link budget study shows that a system with 10-Gbps bit-rate are available assuming the state-of-the-art device performance of the Er-doped fiber amplifier. We further discuss preliminary measurement results of the atmospheric turbulence at the telescope site in Tokyo, and present current study on the design of the key components for the feeder-link laser transceiver.
The Dynamics of Cavitation Bubbles (1949)

Abstract Three regimes of liquid flow over a body are defined, namely: (a) noncavitating flow; (b) cavitating flow with a relatively small number of cavitation bubbles in the field of flow; and (c) cavitating flow with a single large cavity about the body. The assumption is made that, for the second regime of flow, the pressure coefficient in the flow field is no different from that in the noncavitating flow. On this basis, the equation of motion for the growth and collapse of a cavitation bubble containing vapor is derived and applied to experimental observations on such bubbles. The limitations of this equation of motion are pointed out, and include the effect of the finite rate of evaporation and condensation, and compressibility of vapor and liquid. A brief discussion of the role of “nuclei” in the liquid in the rate of formation of cavitation bubbles is also given.
Bloch oscillations in optical waveguide arrays (2002)

Summary form only given.If a DC voltage is applied to a semiconductor superlattice, the arising current may oscillate (Bloch oscillations). Here we report on an optical analog to these Bloch oscillations that reveals special features of the transition from a quasi-continuous model to effects owing to the very discreteness. We consider an array of nearest-neighbor coupled waveguides. In analogy to the DC voltage applied in semiconductor superlattices, the propagation constant of adjacent waveguides shall vary.
Imprecise information and uncertainty in information systems (1990)

Information systems exist to model, store, and retrieve all types of data. Problems arise when some of the data are missing or imprecisely known or when an attribute is not applicable to a particular object. A consistent and useful treatment of such exceptions is necessary. The approach taken here is to allow any attribute value to be a regular precise value, a string denoting that the value is missing, a string denoting that the attribute is not applicable, or an imprecise value. The imprecise values introduce uncertainty into query evaluation, since it is no longer obvious which objects should be retrieved. To handle the uncertainty, two set of objects are retrieved in response to every query: the set of objects that are known to satisfy with complete certainty and the set that possibly satisfies the query with various degrees of uncertainty. Two methods of estimating this uncertainty, based on information theory, are proposed. The measure of uncertainty is used to rank objects for presentation to a user.
RUNX3 Has an Oncogenic Role in Head and Neck Cancer (2009)

Our findings suggest that i) RUNX3 has an oncogenic role in HNSCC, ii) RUNX3 expression observed in HNSCC may be caused in part by demethylation during cancer development, and iii) RUNX3 expression can be a useful marker for predicting malignant behavior and the effect of chemotherapeutic drugs in HNSCC.
High Energy Ultrafast Laser at 2 μm Using Dispersion Engineered Thulium-Doped Fiber (2019)

We report on demonstration of high energy pulse laser at 2 μm by employing a normal dispersion fiber attained by a waveguide dispersion engineering. The normal dispersion fiber has a W-type refractive index profile, with a Thulium(Tm)-doped core. In contrast to a strong anomalous dispersion at 2 μm in a step-index fiber, the design allows strong waveguide dispersion that can generate normal dispersion at the Tm emission band. Mode area scalability of this fiber is discussed under the normal dispersion requirement. The Tm-doped fiber (TDF) is deployed in a ring cavity to produce mode-locked pulses near 2 μm. Subsequently, the pulse is amplified with more than 27 dB gain through the normal dispersion TDF. The output pulse energy reaches up to ~525 nJ at 1852 nm without pulse breaking due to the engineered dispersion. The achieved pulse energy is record high for all-fiber configuration near 2 μm, to our knowledge.
A new approach to the realization of nonrecursive digital filters (1973)

A new realization of nonrecursive digital filters that are used to operate on analog signals is proposed. This realization requires no multiplications, and exploits the relative simplicity of delta modulation as a means for analog to digital conversion. This realization also permits a mechanization as a "very fast" digital filter, using read-only memory (ROM). An evaluation of this realization in terms of computation time storage requirements and mean-squared error is presented. These characteristics are compared with their counterparts for existing realization methods of nonrecursive digital filters. Computer simulation results that tend to confirm the theoretical results of the error analysis are included.
The Automated Tropical Cyclone Forecasting System (Version 3.2) (2000)

The Automated Tropical Cyclone Forecasting System (ATCF) is software intended to automate and optimize much of the tropical cyclone forecasting process. The system features global tracking capability, a suite of objective aids, and a user interface that allows simultaneous tracking of multiple tropical cyclones. The version discussed in this article, ATCF 3.2, runs on UNIX workstations. The Joint Typhoon Warning Center in Guam, the Naval Pacific Meteorology and Oceanography Center in Pearl Harbor, and the Naval Atlantic Meteorology and Oceanography Center in Norfolk successfully used ATCF 3.2 during the 1998 tropical cyclone season.
Rheology and flow behavior of suspensions of nanosized plate‐like particles in polyester resins at the startup of shear flows; Experimental and modeling (2008)

Abstract Applications of organoclays to polymer resins are potentially of great technical interest. This research targets preparation and characterization of nanocomposites of organoclays in an unsaturated polyester resin (UP). The nanocomposites with two distinct dispersion levels were compounded in a complex multisteps mixing process at three concentrations and subsequently their microstructures were characterized by XRD. The solution‐state rheological properties of layered silicate/UP were measured in the start‐up of steady state in the simple shear mode and analyzed based on our observations of internal structure of nanoparticles dispersion. Strong shear thinning behavior caused by increasing particle alignment induced by the shear field was observed for the suspensions. Effects of nanoparticles loadings and shearing on transient viscosity of the UP resin were examined. The experimental results show that increasing shear time in nanosuspension preparation steps and hence improvements of nanoplate dispersion in the polyester resin give rise to viscosity of the suspensions. A theoretical analysis of the motion of rigid ellipsoidal particles in a Newtonian fluid based on the thermodynamic approach and Jeffery's analysis of the motion of ellipsoid particles with an interaction term was developed to determine the orientation state of disc‐shape layers and then, the expression for the extra stress tensor was calculated to predict transient viscosity and normal stress differences. It is found that the thin oblate particles have significant orientation preference in the shearing direction. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers
The effects of subtractive-type speech enhancement/noise reduction algorithms on parameter estimation for improved recognition and coding in high noise environments (2003)

The authors present the results of a study designed to investigate the effects of subtractive-type noise reduction algorithms on LPC-based spectral parameter estimation as related to the performance of speech processors operating with input SNRs of 15 dB and below. Subtractive noise preprocessing greatly improves the SNR, but system performance improvement is not commensurate. LPC spectral estimation is affected by the character of the residual noise which exhibits greater variance and spectral granularity than the original broadband noise. The study shows that removing less than the full amount of noise and whitening it improves spectral estimation and speech device performance. Techniques and performance results are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
GPR37 Surface Expression Enhancement via N-Terminal Truncation or Protein−Protein Interactions (2009)

GPR37, also known as the parkin-associated endothelin-like receptor (Pael-R), is an orphan G-protein-coupled receptor (GPCR) that exhibits poor plasma membrane expression when expressed in most cell types. We sought to find ways to enhance GPR37 trafficking to the cell surface to facilitate studies of GPR37 functional activity in heterologous cells. In truncation studies, we found that removing the GPR37 N-terminus (NT) dramatically enhanced the receptor's plasma membrane insertion. Further studies on sequential NT truncations revealed that removal of the first 210 amino acids increased the level of surface expression nearly as much as removal of the entire NT. In studies examining the effects of coexpression of GPR37 with a variety of other GPCRs, we observed significant increases in the level of GPR37 surface expression when the receptor was coexpressed with adenosine receptor A(2A)R or dopamine receptor D(2)R. Co-immunoprecipitation experiments revealed that full-length GPR37 and, to a greater extent, the truncated GPR37 were capable of robustly associating with D(2)R, resulting in modestly altered D(2)R affinity for both agonists and antagonists. In studies examining potential interactions of GPR37 with PDZ scaffolds, we observed a specific interaction between GPR37 and syntenin-1, which resulted in a dramatic increase in the level of GPR37 surface expression in HEK-293 cells. These findings reveal three independent approaches (N-terminal truncation, coexpression with other receptors, and coexpression with syntenin-1) by which GPR37 surface trafficking in heterologous cells can be greatly enhanced to facilitate functional studies with this orphan receptor.
A genetic therapy for familial hypercholesterolemia. (1990)

The WHHL rabbit serves as an animal model for the human genetic disease, familial hypercholesterolemia. In initial studies aimed at the development of a genetic therapy for familial hypercholesterolemia (i.e., introduction of a normal LDL receptor gene), WHHL rabbit skin fibroblasts were transduced with a retroviral vector expressing a normal human LDL receptor. Correction of the WHHL rabbit genetic defect in vitro was confirmed. Autologous fibroblasts expressing LDL receptors were reimplanted in donor rabbits and were found to survive and express the recombinant receptor in vivo for up to 4 weeks. In vivo LDL receptor expression by autologous cells stably transduced with functioning LDL receptors is possible. Transduction of greater numbers of cells along with increased cell survival in vivo may eventually lead to a specific and effective genetic therapy for familial hypercholesterolemia.
The broad-band Wiener solution for Griffiths-Jim beamformers (1992)

The authors treat the problem of finding the Wiener filters for a wideband adaptive beamformer. Explicit expressions are given for the filters and error power spectrum in the frequency domain. The expressions are simple to program and give the possibility of investigating superresolution for wideband signals and of determining sufficient lengths of the finite-impulse-response filters in adaptive arrays. The major results are an analytical expression for the broadband array Wiener solution given for an arbitrary spectrum for target, interference, and noise and an approximate analytic expression for the angular 3-dB beamwidth for broadband signals.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Heuristic Remarks and Mathematical Problems Regarding the Theory of Connecting Systems (1962)

A connecting system consists of a set of terminals, a control unit for processing call information, and a connecting network. Together, these three elements provide communication, e.g., supply telephone service, among the various terminals. In this paper we present a comprehensive view of the theory of connecting systems, an appraisal of its current status, and some suggestions for further progress. The existing probabilistic theory is reviewed and criticized. The basic features of connecting systems, such as structure, random behavior, complexity, and performance, are discussed in a nontechnical way, and the chief difficulties that beset the construction of a theory of traffic in large systems are described. It is then pointed out that despite their great complexity, connecting systems have a definite structure which can be very useful in analyzing their performance. A natural division of the subject into combinatory, probabilistic, and variational problems is drawn, and is illustrated by discussing a simple problem of each type in detail.
High-power operation of heterobarrier blocking structure InGaAlP visible light laser diodes (1990)

Heterobarrier blocking structure InGaAlP visible light laser diodes employing a thin active layer (0.04 μm) and asymmetry coatings have been fabricated. The high light-output power operation with this heterobarrier blocking structure was investigated. The light-output power versus cw current curve was linear up to 43 mW and a maximum light output power of 51 mW was obtained. A high-power operation such as 20 mW was maintained at 40 °C. Stable oscillation in the fundamental transverse mode was obtained up to 30 mW. These results show that this heterobarrier blocking structure supplies a sufficient current confinement effect even under a high-light output power operation.
Long term complete remission of severe nephrotic syndrome secondary to diffuse global (IV-G) lupus nephritis following autologous, haematopoietic peripheral stem (CD34+) cell transplantation (2006)

Autologous haematopoietic stem cell transplantation has become an accepted powerful therapeutic procedure for patients with severe, intractable SLE. Here we describe a 26-year old patient with stage IV-G diffuse global proliferative lupus nephritis and refractory nephrotic syndrome who responded to autologous peripheral stem cell transplantation (ASCT) after two mobilization procedures. Five years later the patient is in complete clinical and immunologic remission. The indications for ASCT and its mechanism of action are briefly discussed.
Electronic packaging in the 1990s-a perspective from America (1991)

The author reviews current packaging technologies. He starts with the packaging environment in the US, then projects the system requirements into the year 2000 and reviews the base packaging technologies currently in use from consumer electronics to mainframe computers. He ends with projected advanced packaging in all the key technologies: chip-level connections, power distribution, and heat removal from the chip, first-level single-chip and multichip packages, package-to-board interconnections, and second-level packages.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Compressed Sensing Approach for Array Diagnosis From a Small Set of Near-Field Measurements (2011)

A technique for array diagnosis using a small number of measured data acquired by a near-field system is proposed. The technique, inspired by some recent results in the field of compressed sensing, requires the preliminary measurement of a failure-free reference array. The linear system relating the difference between the field measured using the reference array and the field radiated by the array under test, and the difference between the coefficients of the reference and of the AUT array, is solved using a proper regularization procedure. Numerical examples confirm that the technique gives satisfactory results in terms of failure detection with a reduction in the number of data of two orders of magnitudes compared to standard back-propagation technique and of one order of magnitude compared to the number of elements of the array, provided that the number of fault elements is small. This result is relevant in practical applications, since the high cost of large array diagnosis in near-field facilities is mainly caused by the time required for the data acquisition. Accordingly, the technique is particularly suitable for routine testing of arrays.
Lyophilized liposome encapsulated hemoglobin (1994)

These data suggest that lyophilized liposome-encapsulated hemoglobin can be safely administered to conscious rats, supporting the development of this substance as a potential blood substitute.
Primary lung tumors in cats: 86 cases (1979–1994) (1997)

To identify possible occult primary lung tumors, thoracic radiography should be performed on cats with clinical signs of long duration, including weight loss, lethargy, and dyspnea.
Facilitative and functional fats in diets of cats and dogs (2006)

LDL Low-density lipoprotein HDL High-density lipoprotein