gebhart/patrepeval huggingface dataset:
Discovery of Novel Imidazopyridine GSK-3β Inhibitors Supported by Computational Approaches (2020)

The interest of research groups and pharmaceutical companies to discover novel GSK-3β inhibitors has increased over the years considering the involvement of this enzyme in many pathophysiological processes and diseases. Along this line, we recently reported on 1H-indazole-3-carboxamide (INDZ) derivatives <b>1</b>-<b>6</b>, showing good GSK-3β inhibition activity. However, they suffered from generally poor central nervous system (CNS) permeability. Here, we describe the design, synthesis, and in vitro characterization of novel imidazo[1,5-a]pyridine-1-carboxamide (IMID 1) and imidazo[1,5-a]pyridine-3-carboxamide (IMID 2) compounds (<b>7</b>-<b>18</b>) to overcome such liability. In detail, structure-based approaches and fine-tuning of physicochemical properties guided the design of derivatives <b>7</b>-<b>18</b> resulting in ameliorated absorption, distribution, metabolism, and excretion (ADME) properties. A crystal structure of <b>16</b> in complex with GSK-3β enzyme (PDB entry 6Y9S) confirmed the in silico models. Despite the nanomolar inhibition activity, the new core compounds showed a reduction in potency with respect to INDZ derivatives <b>1</b>-<b>6</b>. In this context, Molecular Dynamics (MD) and Quantum Mechanics (QM) based approaches along with NMR investigation helped to rationalize the observed structure activity relationship (SAR). With these findings, the key role of the acidic hydrogen of the central core for a tight interaction within the ATP pocket of the enzyme reflecting in good GSK-3β affinity was demonstrated.
Controlled synthesis and structural stability of alginate-based nanofibers (2007)

Electrospinning has emerged as a unique and versatile technique for the fabrication of nanofibrous structures with well-defined architecture to mimic the native extracellular matrix for tissue engineering applications. In this study, natural polymer alginate-based nanofibers were fabricated by electrospinning blend solutions of alginate and polyethylene oxide (PEO). To obtain better fibrous morphology and structural uniformity, the influence of alginate/PEO ratio and surfactants on the electrospun products were investigated. This study elucidated that polymer solution viscosity is a key factor that regulates the electrospinnability of the solution and the structure of the electrospun product. The sustained structural integrity of nanofibers in aqueous environments as well as simulated body fluid, which is essential for tissue engineering applications, was improved by crosslinking. This study also revealed that the polymer solution properties and thus the solution spinnability changed over storage time in the ambient environment, which can be a major source in causing the problem of reproducibility or resulting in differed structures when the solution is electrospun at different times. In light of the general biocompatibility of alginate, the technical approaches introduced and the underlying mechanisms revealed in this study may be of benefit to the production of alginate-based nanofibrous matrices for a wide range of tissue engineering applications.
Method and system for enhancing microbial motility (1990)

A method and system for enhancing the motility of microorganisms by placing an effective amount of chlorinated hydrocarbons, preferably chlorinated alkenes, and most preferably trichloroethylene in spaced relation to the microbes so that the surprisingly strong, monomodal, chemotactic response of the chlorinated hydrocarbon on subsurface microbes can draw the microbes away from or towards and into a substance, as desired. In remediation of groundwater pollution, for example, TCE can be injected into the plume to increase the population of microbes at the plume whereby the plume can be more quickly degraded. A TCE-degrading microbe, such as Welchia alkenophilia, can be used to degrade the TCE following the degradation of the original pollutant.
Injection-Locked Mode-Locked Laser With Long-Term Stabilization and High Power-per-Combline (2008)

A novel method is presented to provide long-term stabilization of an injection-locked harmonically mode-locked laser to a narrow linewidth continuous-wave (CW) source for the first time. The method, based on the Pound-Drever-Hall method of laser frequency stabilization, exploits the phase shift across a laser cavity mode resonance to detect the offset between the CW frequency and the combline frequency desired for injection-locking. Long-term suppression of the radio-frequency supermode noise spurs is shown as well as 36-dB suppression of optical supermodes. Significant reductions in phase and amplitude noise are also shown due to injection. Postamplification noise results are presented, showing an increase in optical power per combline with no degradation in pulse-to-pulse energy fluctuation or timing jitter.
Low-noise picosecond soliton transmission by use of concatenated nonlinear amplifying loop mirrors (1997)

We compare two systems that are specially configured with loop mirrors to provide stable picosecond soliton transmission. One configuration, created by Smith Doran [J. Opt. Soc. Am. B12, 1117 (1995)], uses nonlinear optical loop mirrors. This configuration is compared with another that uses nonlinear amplifying loop mirrors, the configuration of which we systematically determine from the amplitude and the pulse-width switching characteristics of the nonlinear optical loop mirror. It is found that the nonlinear optical loop mirror configuration allows stable pulse transmission with much less dispersive background waves than does the nonlinear optical loop mirror configuration. This clean performance is obtained at the cost of slightly lessening the parameter region of global stability of pulses. A technique for accurately estimating the region of global stability for amplitude and pulse-width perturbations of the stable pulse is also given.
Towards an Epitope-Based Human Vaccine for Influenza (2005)

The conventional, currently available vaccines against influenza virus, though quite successful, suffer from a few shortcomings; one major limitation is their restriction to the specific strains that are included in the vaccine. We review herewith some of the more recently developed influenza vaccines and further describe our own results on the design of epitope-based vaccine for human use. In this vaccine, a combination of B- and T-cell epitopes are individually expressed within an immunogenic molecule--salmonella flagellin--and the resultant recombinant flagella serve both as a carrier and as an adjuvant. The mixture of recombinant flagella expressing the appropriate epitopes was administered to young and aged mice as well as to human/mouse chimera model in which human PBMC are functioning within the mice body. Intranasal immunization in all these animal models led to effective protection against challenge infection with different strains of influenza virus.
Expanding the Family of Collagen Proteins: Recombinant Bacterial Collagens of Varying Composition Form Triple-Helices of Similar Stability (2009)

The presence of the (Gly-Xaa-Yaa)(n) open reading frames in different bacteria predicts the existence of an expanded family of collagen-like proteins. To further explore the triple-helix motif and stabilization mechanisms in the absence of hydroxyproline (Hyp), predicted novel collagen-like proteins from Gram-positive and -negative bacteria were expressed in Escherichia coli and characterized. Soluble proteins capable of successful folding and in vitro refolding were observed for collagen proteins from Methylobacterium sp 4-46, Rhodopseudomonas palustris and Solibacter usitatus . In contrast, all protein constructs from Clostridium perfringens were found predominantly in inclusion bodies. However, attachment of a heterologous N-terminal or C-terminal noncollagenous folding domain induced the Clostridium perfringens collagen domain to fold and become soluble. The soluble constructs from different bacteria had typical collagen triple-helical features and showed surprisingly similar thermal stabilities despite diverse amino acid compositions. These collagen-like proteins provide a resource for the development of biomaterials with new properties.
Activity-based probes for functional proteomics (2002)

Achieving an understanding of the functional role of all proteins expressed by a complex organism will require the development of methods that enable the rapid monitoring of protein function on a global scale. Current genomics and proteomics technologies fall short of this goal since they measure only the relative abundance of transcripts and proteins, respectively. Recent efforts in several laboratories have led to the development of tagged chemical probes that selectively react with families of active enzymes based on shared mechanistic features. These activity-based probes (ABPs) permit the quantitation and comparison of multiple protein activities simultaneously in complex proteomes. In this paper, the general properties and design features of ABPs will be discussed with an emphasis on the use of ABPs for activity-based proteome analysis.
A novel food-based negative oral contrast agent compared with two conventional oral contrast agents in abdominal CT: a three-arm parallel blinded randomised controlled single-centre trial (2022)

EudraCT (2017-002368-42) and in ClinicalTrials.gov (NCT03326518).
Multi-touch Multi-user Interactive Control System Using Mobile Devices (2013)

The penetration of multi-touch devices have created a new generation of users comfortable with the gestures associated with such devices. Developers have already embraced such trends by capturing and handling them in their applications. We propose a novel approach to use mobile devices as system controls for applications. Unlike existing approaches, our solution has three key features. First, it is flexible to customize for different applications. Second, it allows multiple users to interact with the application as well as to interact with each other. Third, it fully supports multi-touch and user-defined gestures. The feasibility of our solution is demonstrated through the implementation test we have made for web applications.
Antiviral Activities of Novel 5-Phosphono-Pent-2-en-1-yl Nucleosides and Their Alkoxyalkyl Phosphonoesters (2006)

Three acyclic nucleoside phosphonates are currently approved for clinical use against infections caused by cytomegalovirus (Vistide), hepatitis B virus (Hepsera), and human immunodeficiency virus type 1 (Viread). This important antiviral class inhibits viral polymerases after cellular uptake and conversion to their diphosphates, bypassing the first phosphorylation, which is required for conventional nucleoside antivirals. Small chemical alterations in the acyclic side chain lead to marked differences in antiviral activity and the spectrum of activity of acyclic nucleoside phosphonates against various classes of viral agents. We synthesized a new class of acyclic nucleoside phosphonates based on a 5-phosphono-pent-2-en-1-yl base motif in which the oxygen heteroatom usually present in acyclic nucleoside phosphonates has been replaced with a double bond. Since the intrinsic phosphonate moiety leads to low oral bioavailability and impaired cellular penetration, we also prepared the hexadecyloxypropyl esters of the 5-phosphono-pent-2-en-1-yl nucleosides. Our earlier work showed that this markedly increases antiviral activity and oral bioavailability. Although the 5-phosphono-pent-2-en-1-yl nucleosides themselves were not active, the hexadecyloxypropyl esters were active against DNA viruses and hepatitis B virus, in vitro. Notably, the hexadecyloxypropyl ester of 9-(5-phosphono-pent-2-en-1-yl)-adenine was active against hepatitis B virus mutants resistant to lamivudine, emtricitabine, and adefovir.
Refereeing conflicts in hardware transactional memory (2009)

In the search for high performance, most transactional memory (TM) systems execute atomic blocks concurrently and must thus be prepared for data conflicts. The TM system also needs to choose a policy to decide when and how to manage the resulting contention. In this paper, we analyze the interplay between conflict resolution time and contention management policy in the context of hardware-supported TM systems, highlighting both the implementation tradeoffs and the performance implications of the various points in the design space. We show that both policy decisions have a significant impact on the ability to exploit available parallelism and thereby affect overall performance. Our analysis corroborates previous research findings that stalling (especially prior to retrying an access rather than the entire transaction) helps side-step conflicts and avoid wasted work. We also demonstrate that conflict resolution time has the dominant effect on performance: lazy (which delays resolution to commit time) uncovers more parallelism than eager (which resolves conflicts at access time). Furthermore, Lazy's delayed conflict management decreases the likelihood of livelock while Eager needs sophisticated priority mechanisms. Finally, we evaluate a mixed conflict detection mode that detects write-write conflicts eagerly while detecting read-write conflicts lazily, and show that it provides a good compromise between flexibility and implementation complexity.
Spatial chirp control of high-intensity 4D pulse focusing for laser-matter interactions (2013)

Spatial chirp can be manipulated to control the focusing conditions for materials processing. Our double-ABCD nonparaxial analysis helps to understand and exploit the mechanisms for intensity localization, pulse front tilt, and grating formation, and includes initial spectral phase and detuning of the wavelength crossing plane. We also present a novel method for creating high density, high intensity interference patterns with crossed beams that have no relative pulse front tilt.
Conversion of Cheese Whey and Whey Permeate to Oil and Single-Cell Protein (1978)

Cheese whey and ultrafihration permeate were used as media for producing oil and single-cell protein with two strains each of the yeasts Candida curvata and Tricbosporon cutaneum.Optimum temperatures for cell multiplication and oil production by the four yeasts ranged from 28 to 33 C. Optimum pH's for cell multiplication were from 5.4 to 5.8. The optimum pH for oil production differed slightly from that for cell multiplication. Greater cell numbers were obtained if ammonium hydroxide was added to the medium, and mineral supplements also were sometimes stimulatory. Fermentation of whey by these organisms for 60 h reduced the chemical oxygen demand of the medium by a maximum of 85%, produced (depending on the organism) 6.3 to 9.3 g of oil/liter of whey, and left most of the protein unused. Fermentation of permeate for 72 h reduced chemical oxygen demand 95% and produced (depending on the organism) 4.0 to 15.6 g oil, 19.6 to 26.8 g cells, and 2.2 to 3.2 g single-cell protein/liter of permeate. The two strains of C. curvata were the most efficient in producing oil and reducing oxygen demand. The fat contained oleic (~50%), palmitic (~30%), stearic (%15%), and linoleic (~8%) acids. The cell protein was rich in methionine and other essential amino acids except that the two C. curvata strains were deficient in lysine.
Synthesis of trisubstituted thiophenes designed as progesterone receptor modulator (2006)

When a known 2-[4-morpholino]-3-aryl-5-substituted thiophene, which showed moderate activity as a progesterone antagonist, was superimposed with a potent steroidal progesterone antagonist Org-33628, it showed a fair alignment in most parts of the molecules. According to the molecular modelling, displacement of the morpholine oxygen atom in the thiophene derivative with a carbonyl group would provide a better alignment with the C-3 carbonyl in Org-33628. Thus, a series of novel trisubstituted thiophenes bearing a cyclic ketone moiety was synthesized. Although these compounds only showed weak activities as progesterone receptor antagonists, all target compounds are novel and are fully characterized.
Nonlinear Optics and Crystalline Whispering Gallery Mode Cavities (2004)

We demonstrate parametric frequency doubling in a whispering gallery cavity made of periodically poled lithium niobate. This demonstration is an example of utility of such crystalline optical whispering gallery resonators with very high Q factors, which we have fabricated.
Evaluation of a modified-live virus vaccine administered in ovo to protect chickens against Newcastle disease (1993)

The B1 strain of Newcastle disease virus (NDV-B1), which is nonpathogenic for newly hatched chickens, killed embryos when it was used to inoculate chicken eggs at embryonation day 18. Treatment of NDV-B1 with an alkylating agent, ethylmethane sulfonate (EMS) markedly reduced the pathogenicity of the virus for 18-day-old chicken embryos. Eggs inoculated with the modified virus (NDV-B1-EMS) hatched, and the virus was isolated from lungs and spleen of 1-day-old chickens. The hatched chickens developed antibody to NDV and were protected against challenge exposure (at 4 weeks of age) with a highly virulent GB-Texas strain of NDV. Presence of maternal antibody to NDV in embryonating eggs did not influence the protective ability of NDV-B1-EMS, which also induced protective immunity when administered to 4-week-old chickens. The 50% protective dose of NDV-B1-EMS in maternal antibody-negative and -positive embryos was calculated to be 10.77 and 17.70 embryo 50% lethal doses, respectively. Results of the study indicated that NDV-B1-EMS may be used as an embryo vaccine to protect chickens against Newcastle disease.
Molecular Simulation Study of Peptide Amphiphile Self-Assembly (2008)

We study the self-assembly of peptide amphiphile (PA) molecules, which is governed by hydrophobic interactions between alkyl tails and a network of hydrogen bonds between peptide blocks. We demonstrate that the interplay between these two interactions results in the formation of assemblies of different morphology, in particular, single beta-sheets connected laterally by hydrogen bonds, stacks of parallel beta-sheets, spherical micelles, micelles with beta-sheets in the corona, and long cylindrical fibers. We characterize the size distribution of the aggregates as a function of the molecular interactions. Our results suggest that the formation of nanofibers of peptide amphiphiles obeys an open association model, which resembles living polymerization.
Comparative characteristics of iron-core current transformers and Rogowski Coils for applications for protective relaying purposes (2009)

This paper compares the operating characteristics of non-conventional current sensors, Rogowski Coils, and conventional iron-core current transformers for protective relaying applications.
A 4.8GB/s 256Mb(x16) Reduced-Pin-Count DRAM and Controller Architecture (RPCA) to Reduce Form-Factor & Cost for IOT/Wearable/TCON/Video/AI-Edge Systems (2019)

A new breed of Form-Factor-Driven DRAMs offers 80% lower standby power and > 50% IO signal reduction vs. Capacity-Driven commodity DRAM. Command/address/data are multiplexed onto 16 pins and combined with a Serial Control Pin in a Single-Edge-Pinout-Floorplan, providing bus efficiency >98%. Major SOC-DRAM subsystem cost savings are enabled via die size, packaging and PCB area savings using this RPCA. A 100× speedup of array fills using a new Group Write circuit further reduces test cost.
Higher-order predistortion linearisation using cascaded lower-order nonlinearities (2004)

A technique for realising nonlinear functions of order ≥5 using cascaded third-order nonlinear functions is described. The technique can be used to efficiently generate higher-order nonlinearities for predistortion linearisation applications. The use of two cascaded third-order functions is experimentally demonstrated to be comparable to a fifth-order implementation in performance.
Harsh environments minimally invasive optical sensor using free-space targeted single-crystal silicon carbide (2006)

To the best of our knowledge, for the first time, a single-crystal silicon carbide (SiC)-based minimally invasive smart optical sensor suited for harsh environments has been designed and demonstrated. The novel sensor design is based on an agile wavelength source, instantaneous single-wavelength strong two-beam interferometry, full optical power cycle data acquisition, free-space targeted laser beams, multiple single-crystal-thick SiC optical front-end chips, and multiwavelength signal processing for unambiguous temperature measurements to form a fast and distributed smart optical sensor system. Experiments conducted using a 1550-nm eye-safe band-tunable laser and a 300-/spl mu/m coating-free thick SiC chip demonstrate temperature sensing from room temperature to 1000/spl deg/C with an estimated average 1.3/spl deg/C resolution. Applications for the proposed sensor include use in fossil fuel-based power systems, aerospace/aircraft systems, satellite systems, deep-space exploration systems, and drilling and oil mining industries.
A Mitochondrial DNA Mutation as a Cause of Leber's Hereditary Optic Neuropathy (1989)

Leber's hereditary optic neuropathy is a maternally inherited disease associated with the late onset of bilateral loss of central vision and cardiac dysrhythmias. The maternal inheritance is explained by the mitochondrial origin of the disease. Analysis of the sequence of a mitochondrial DNA has indicated that a single nucleotide change at position 11778 is associated with this disease. This mutation converts the 340th amino acid of NADH dehydrogenase subunit 4 from an arginine to a histidine and eliminates an SfaNI endonuclease restriction site. A survey of restriction-fragment-length polymorphisms in the mitochondrial DNA of three independent families with this disease (an American black and two white European families) and 10 controls confirmed that this SfaNI site is associated with the disease. A phylogenetic tree for mitochondrial DNA polymorphism and sequence variants from three probands with Leber's disease and four controls was constructed, and the mutation at position 11778 was found to be associated with two mitochondrial DNA backgrounds--an American black mitochondrial DNA and a European mitochondrial DNA. Thus, this mutation must have arisen twice independently. Since the mutation correlated with symptoms of Leber's disease in both cases, these findings indicate that the mutation is a cause of the disease. This genetic analysis has identified the specific point mutation in the mitochondrial DNA that results in Leber's hereditary optic neuropathy.
High-Density Magneto-Optical Recording with a Reduced-Size Optical Spot. (2001)

In this paper, we examine the influence of the optical spot diameter on the magneto-optical recording properties. An optical spot with a reduced diameter of 380 nm was obtained by using a semiconductor blue laser and a solid immersion lens. As a medium, we used magnetic bilayer media, which can be read with GMR heads and are available for hybrid recording. It was proved that the shrinkage of the spot considerably changed the recording properties. Calculation based on Huth’s theory explained the increase in the shrinking force that acts on the domain wall. This increase is mainly caused by the steeper temperature variation in the focused spot. However, this force can be compensated for by controlling the film composition, and we successfully wrote domains with a diameter of 30% of the recording optical spot diameter.