gebhart/patrepeval huggingface dataset:
The Azide Method in Peptide Synthesis: Its Scope and Limitations1 (1974)

The chemistry, scope, and limitations of the azide method of peptide synthesis are discussed with special emphasis on side reactions encountered during the preparation of hydrazides, azides, and in the coupling process. Curtius rearrangement, racemization, and amide formation are part of the discussion. 1. The Formation of Hydrazides 2. Side Reactions in the Preparation of Hydrazides 3. The Preparation of Azides from Hydrazides 4. Side Reactions during Azide Formation 5. Acylation with Azides 6. Side Reactions in Azide Coupling 7. Modifications of the Azide Method 7.1. The Honzl-Rudinger Method 7.2. The Medzihradszky Method 8. Racemization in Coupling with Azides 9. The Azide Method in Solid-Phase Peptide Synthesis 9.1. The Preparation of Peptide Hydrazides 9.2. The Building of Peptide Chains 10. Cyclization with the Azide Method 11. Polymerization by the Azide Method 12. Acyldiimides
X‐ray crystal structure of cytochrome P450 monooxygenase CYP101J2 fromSphingobium yanoikuyaestrain B2 (2016)

The cytochrome P450 monooxygenases (P450s) catalyze a vast array of oxygenation reactions that can be useful in biocatalytic applications. CYP101J2 from Sphingobium yanoikuyae is a P450 that catalyzes the hydroxylation of 1,8-cineole. Here we report the crystallization and X-ray structure elucidation of recombinant CYP101J2 to 1.8 Å resolution. The CYP101J2 structure shows the canonical P450-fold and has an open conformation in the absence of substrate. Analysis of the structure revealed that CYP101J2, in the absence of substrate, forms a well-ordered substrate-binding channel that suggests a unique form of substrate guidance in comparison to other bacterial 1,8-cineole-hydroxylating P450 enzymes. Proteins 2017; 85:945-950. © 2016 Wiley Periodicals, Inc.
Protein Kinase A-dependent Phosphorylation of Rap1 Regulates Its Membrane Localization and Cell Migration (2013)

The small G protein Rap1 can mediate "inside-out signaling" by recruiting effectors to the plasma membrane that signal to pathways involved in cell adhesion and cell migration. This action relies on the membrane association of Rap1, which is dictated by post-translational prenylation as well as by a stretch of basic residues within its carboxyl terminus. One feature of this stretch of acidic residues is that it lies adjacent to a functional phosphorylation site for the cAMP-dependent protein kinase PKA. This phosphorylation has two effects on Rap1 action. One, it decreases the level of Rap1 activity as measured by GTP loading and the coupling of Rap1 to RapL, a Rap1 effector that couples Rap1 GTP loading to integrin activation. Two, it destabilizes the membrane localization of Rap1, promoting its translocation into the cytoplasm. These two actions, decreased GTP loading and decreased membrane localization, are related, as the translocation of Rap1-GTP into the cytoplasm is associated with its increased GTP hydrolysis and inactivation. The consequences of this phosphorylation in Rap1-dependent cell adhesion and cell migration were also examined. Active Rap1 mutants that lack this phosphorylation site had a minimal effect on cell adhesion but strongly reduced cell migration, when compared with an active Rap1 mutant that retained the phosphorylation site. This suggests that optimal cell migration is associated with cycles of Rap1 activation, membrane egress, and inactivation, and requires the regulated phosphorylation of Rap1 by PKA.
Effects of a piezoelectric based nonlinear energy sink on the behavior of an electromechanically coupled beam (2018)

Various researchers have investigated the behavior of a linear oscillator weakly coupled to a nonlinear mechanical attachment that has essential stiffness nonlinearity. Under certain conditions, the essentially nonlinear attachment can act as a nonlinear energy sink (NES) and the irreversible transfer of vibration energy from a main structure to the nonlinear attachment is observed. Another characteristic of an essentially nonlinear attachment is the nonexistence of a resonance frequency. Therefore, nonlinear energy sinks have increased robustness against detuning. While mechanical nonlinear attachments are usually linked to a host structure by nonlinear mechanical elements, linear coupling (piezoelectric transduction) is observed in piezoelectric based nonlinear energy sinks and nonlinearity can be achieved through electrical circuit design. This work presents an experimentally validated piezoelectric based nonlinear energy sink. An essentially nonlinear piezoelectric shunt circuit and its practical realization are discussed in detail. The circuit nonlinear behavior and the performance of the piezoelectric nonlinear energy sink to attenuate vibrations of a cantilever over a wide range of frequencies are experimentally validated.
Silicon micro-resonators for on-chip optical networks (2008)

Recent results on compact silicon photonic circuits employing micro-resonators is reported including optical delay lines, electro-optic modulators, broadband optical switches, wavelength filters, etc..
Maternal obesity in sheep impairs foetal hepatic mitochondrial respiratory chain capacity (2020)

The data indicate that MO impairs foetal hepatic mitochondrial oxidative capacity and affects total mitochondrial phospholipid content. In addition, MO affects the regulation of foetal liver redox pathways, indicating metabolic adaptations to the higher foetal lipid environment. Consequences of in utero programming of foetal hepatic metabolism may persist and compromise mitochondrial bioenergetics in later life, and increase susceptibility to metabolic diseases.
On the reliability of correlation based stereo matching (2002)

Techniques for enhancing the reliability of correlation- based stereo matching are described. A confidence factor is introduced to evaluate the accuracy of a match measure and to isolate the areas where the matching algorithm fails to provide correct results. Contrast and spatial frequency content, which are major factors affecting the matchability of neighborhoods, are incorporated in the match measure as the confidence factor. The resulting match score should be more useful in determining the areas requiring interpolation and the smoothness of the interpolated values in the removal of bad matches
AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia (2015)

Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2–6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2–6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2–6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene.
In vitro tools for orally inhaled drug products—state of the art for their application in pharmaceutical research and industry and regulatory challenges (2021)

Abstract The drug development process is a lengthy and expensive challenge for all involved players. Experience with the COVID-19 pandemic underlines the need for a rapid and effective approval for treatment options. As essential prerequisites for successful drug approval, a combination of high-quality studies and reliable research must be included. To this day, mainly in vivo data are requested and collected for assessing safety and efficacy and are therefore decisive for the pre-clinical evaluation of the respective drug. This review aims to summarize the current state of the art for safety and efficacy studies in pharmaceutical research and industry to address the relevant regulatory challenges and to provide an outlook on implementing more in vitro methods as alternative to animal testing. While the public demand for alternative methods is becoming louder, first examples have meanwhile found acceptance in relevant guidelines, e.g. the OECD guidelines for skin sensitizer. Besides ethically driven developments, also the rather low throughput and relatively high costs of animal experiments are forcing the industry towards the implementation of alternative methods. In this context, the development of orally inhaled drug products is particularly challenging due to the complexity of the lung as biological barrier and route of administration. The replacement of animal experiments with focus on the lungs requires special designed tools to achieve predictive data. New in vitro test systems of increasing complexity are presented in this review. Limits and advantages are discussed to provide some perspective for a future in vitro testing strategy for orally inhaled drug products. Graphical abstract
Successful detection, expression and purification of the alternatively spliced truncated Sm14 antigen of an Egyptian strain ofSchistosoma mansoni (2014)

Schistosoma mansoni causes intestinal schistosomiasis, a disease that is prevalent in several regions worldwide. To date, a protective vaccine against S. mansoni is still lacking. Several promising antigens have been discovered and evaluated for vaccine protection, such as Sm14 and Sm28GST. In this short communication, we report the successful detection of an alternatively spliced truncated form of Sm14 which was highly expressed in an Egyptian strain of S. mansoni. This truncated Sm14 (TrSm14) protein was formerly reported to be practically non-existent and its complementary DNA (cDNA) was thought to be 'a rare misprocessing of mRNA precursor'. Our finding demonstrates that there is inter-strain variation in the S. mansoni transcriptome and subsequently in the role/function of the expressed proteins. We expressed TrSm14 successfully in Escherichia coli as a fusion protein with the schistosomal antigen Sm28GST. The fusion protein was purified using metal affinity chromatography and was found to be reactive with serum from S. mansoni-infected patients. This suggests a possible diagnostic value for this protein in detection of anti-schistosomal antibodies. In addition, this fusion protein could offer a potential bivalent vaccine candidate against S. mansoni that is worthy of further investigation.
BAGE Hypomethylation Is an Early Event in Colon Transformation and Is Frequent in Histologically Advanced Adenomas (2009)

We showed earlier that BAGE (B melanoma antigen) loci are hypermethylated in normal tissues and hypomethylated in 98% of human cancers. More recently, we provided evidence that hypomethylation of BAGE loci represents an informative marker for colon cancer detection. In this study, we show that hypomethylation of BAGE loci was an early event that occurred in 43% of colorectal adenomas. Interestingly, hypomethylation of BAGE loci was frequent (50%) in tubulo-villous and villous adenomas, these adenomas having a high probability of being transformed into colorectal cancers.
Analyzing the Impact of Access Point Density on the Performance of Finite-Area Networks (2015)

Assuming a network of infinite extent, several researchers have analyzed small-cell networks using a Poisson point process (PPP) location model, leading to simple analytic expressions. The general assumption has been that these results apply to finite-area networks as well. However, do the results of infinite-area networks apply to finite-area networks? In this paper, we answer this question by obtaining an accurate approximation for the achievable signal-to-interference-plus-noise ratio (SINR) and user capacity in the downlink of a finite-area network with a fixed number of access points (APs). The APs are uniformly distributed within the area of interest. Our analysis shows that, crucially, the results of infinite-area networks are very different from those for finite-area networks of low-to-medium AP density. Comprehensive simulations are used to illustrate the accuracy of our analysis. For practical values of signal transmit powers and AP densities, the analytic expressions capture the behavior of the system well. As an added benefit, the formulations developed here can be used in parametric studies for network design. Here, the analysis is used to obtain the required number of APs to guarantee a desired target capacity in a finite-area network.
Multi-dimensional fluorescence lifetime measurements (2007)

In this study, we present two different approaches that allow multi-wavelength fluorescence lifetime measurements in the time domain. One technique is based on a streak camera system, the other technique is based on a time-correlated singlephoton- counting (TCSPC) approach. The setup consists of a confocal laser-scanning microscope (LSM 510, Zeiss) and a Titanium:Sapphire-laser (Mira 900D, Coherent) that is used for pulsed one- and two-photon excitation. Fluorescence light emitted by the sample is dispersed by a polychromator (250is, Chromex) and recorded by a streak camera (C5680 with M5677 sweep unit, Hamamatsu Photonics) or a 16 channel TCSPC detector head (PML-16, Becker & Hickl) connected to a TCSPC imaging module (SPC-730/SPC-830, Becker & Hickl). With these techniques it is possible to acquire fluorescence decays in several wavelength regions simultaneously. We applied these methods to Förster resonance energy transfer (FRET) measurements and discuss the advantages over fluorescence techniques that are already well established in the field of confocal microscopy, such as spectrally resolved intensity measurements or single-wavelength fluorescence lifetime measurements.
SU‐G‐JeP4‐11: Prospective Treatment Plan‐Specific Action Limits for Real‐Time Intrafractional Monitoring in Surface Image Guided Radiosurgery (2016)

Purpose: Surface image‐guided radiosurgery action limits are created to determine when intrafractional patient motion warrants intervention. Action limits remain constant across patients despite plan‐specific effects on brain metastases target coverage. The purpose of this work was twofold: 1) characterize the sensitivity of single‐met per iso and multi‐met per iso treatment plans to motion, and 2) describe a method to prospectively determine plan‐specific action limits considering this sensitivity. Methods: Seventy‐two brain metastases were used for this study. Twenty‐five were treated individually (“single‐met per iso plans”), and 47 were treated simultaneously with at least one other met (“multi‐met per iso plans”). For each met, the proportion of the gross tumor volume that remained within the 100% prescription isodose line after various combinations of translations and rotations (0.0–3.0 mm and 0.0–3.0°) was estimated. This was achieved using code developed in the Matlab environment that exhaustively evaluated the effects of all combinations of translations and rotations in this range. The target volume and the prescription dose volume were considered concentric spheres that encompassed volumes determined from the treatment plan. Plan‐specific contour plots and DVHs were created to illustrate the sensitivity of a specific lesion to motion. Results: Both single‐met per iso and multi‐met per iso plans exhibited compromised target coverage after transformations, though multi‐met per iso plans were considerably more sensitive to motion (2.3% and 39.8%, respectively). Plan‐specific contour plots and DVHs illustrate how size, distance from isocenter, and planning technique affect motion sensitivity. Conclusion: Stereotactic radiosurgery treatment plans that treat multiple brain metastases using a common isocenter are particularly susceptible to patient motion. This technique and other plan‐specific factors should influence motion management. A graphical representation of the sensitivity of any plan to motion can be generated to determine appropriate action limit.
Clinically Established Hemostatic Scaffold (Tissue Fleece) as Biomatrix in Tissue- and Organ-Engineering Research (2003)

Various types of three-dimensional matrices have been used as basic scaffolds in myocardial tissue engineering. Many of those are limited by insufficient mechanical function, availability, or biocompatibility. We present a clinically established collagen scaffold for the development of bioartificial myocardial tissue. Neonatal rat cardiomyocytes were seeded into Tissue Fleece (Baxter Deutschland, Heidelberg, Germany). Histological and ultrastructural examinations were performed by DAPI and DiOC(18) staining and electron microscopy, respectively. Force measurements from the spontaneously beating construct were obtained. The constructs were stimulated with agents such as adrenalin and calcium, and by stretching. Passive stretch curves were obtained. Spontaneous contractions of solid bioartificial myocardial tissue (BMT), 20 x 15 x 2 mm, resulted. Contractions continued to week 12 (40% of BMTs) in culture. Histology revealed intercellular and also cell-fibril junctions. Elasticity was similar to that of native rat myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. Stretch led to the highest levels of contractile force. In summary, bioartificial myocardial tissue with significant in vitro longevity, spontaneous contractility, and homogeneous cell distribution was produced using Tissue Fleece. Tissue Fleece constitutes an effective scaffold to engineer solid organ structures, which could be used for repair of congenital defects or replacement of diseased tissue.
Inhibitory effect of the salmosin gene transferred by cationic liposomes on the progression of B16BL6 tumors. (2003)

Salmosin is a novel disintegrin containing the Arg-Gly-Asp sequence that significantly inhibits platelet aggregation, basic fibroblast growth factor-induced endothelial cell proliferation, and tumor progression by antagonizing integrin-mediated cell interactions. Previously, it was shown that daily administration of salmosin was able to inhibit tumor-derived angiogenesis and adherence and proliferation of tumor cells, resulting in suppression of tumor progression. However, it is very difficult to maintain a therapeutic level of salmosin in the blood by systemic administration of the protein. Hence, an alternative strategy for antiangiogenic cancer therapy, based on the in vivo expression of the salmosin gene administered with cationic liposomes, was investigated. The salmosin peptides expressed in vitro inhibited the proliferation of bovine capillary endothelial cells in a dose-dependent manner, presumably as a result of inhibition of cell adhesion mediated via alpha(v)beta(3) integrin. Subcutaneous administration of the salmosin gene resulted in systemic expression of the gene product and concomitant inhibition of the growth of B16BL6 melanoma cells. Suppression of pulmonary metastases, verified by experimental and spontaneous metastasis models in mice, also resulted from salmosin gene treatment. These results suggest that administration of the salmosin gene complexed to cationic liposomes is effective in maintaining antiangiogenic salmosin at an effective therapeutic level and may be clinically applicable to anticancer gene therapy.
Acquisition, Transport, and Storage of Iron by Pathogenic Fungi (1999)

Iron is required by most living systems. A great variety of means of acquisition, avenues of uptake, and methods of storage are used by pathogenic fungi to ensure a supply of the essential metal. Solubilization of insoluble iron polymers is the first step in iron assimilation. The two methods most commonly used by microorganisms for solubilization of iron are reduction and chelation. Reduction of ferric iron to ferrous iron by enzymatic or nonenzymatic means is a common mechanism among pathogenic yeasts. Under conditions of iron starvation, many fungi synthesize iron chelators known as siderophores. Two classes of compounds that function in iron gathering are commonly observed: hydroxamates and polycarboxylates. Two major responses to iron stress in fungi are a high-affinity ferric iron reductase and siderophore synthesis. Regulation of these two mechanisms at the molecular level has received attention. Uptake of siderophores is a diverse process, which varies among the different classes of compounds. Since free iron is toxic, it must be stored for further metabolic use. Polyphosphates, ferritins, and siderophores themselves have been described as storage molecules. The iron-gathering mechanisms used by a pathogen in an infected host are largely unknown and can only be posited on the basis of in vitro studies at present.
ACCURATE SHORT-TERM ANALYSIS OF THE FUNDAMENTAL FREQUENCY AND THE HARMONICS-TO-NOISE RATIO OF A SAMPLED SOUND (1993)

We present a straightforward and robust algorithm for periodicity detection, working in the lag (autocorrelation) domain. When it is tested for periodic signals and for signals with additive noise or jitter, it proves to be several orders of magnitude more accurate than the methods commonly used for speech analysis. This makes our method capable of measuring harmonics-to-noise ratios in the lag domain with an accuracy and reliability much greater than that of any of the usual frequency-domain methods. By definition, the best candidate for the acoustic pitch period of a sound can be found from the position of the maximum of the autocorrelation function of the sound, while the degree of periodicity (the harmonics-to-noise ratio) of the sound can be found from the relative height of this maximum. However, sampling and windowing cause problems in accurately determining the position and height of the maximum. These problems have led to inaccurate timedomain and cepstral methods for pitch detection, and to the exclusive use of frequency-domain methods for the determination of the harmonics-to-noise ratio.