gebhart/patrepeval huggingface dataset:
Complex Loop Dynamics Underpin Activity, Specificity and Evolvability in the (βα)8 Barrel Enzymes of Histidine and Tryptophan Biosynthesis (2022)

Enzymes are conformationally dynamic, and their dynamical properties play an important role in regulating their specificity and evolvability. In this context, substantial attention has been paid to the role of ligand-gated conformational changes in enzyme catalysis; however, such studies have focused on tremendously proficient enzymes such as triosephosphate isomerase and orotidine 5’-monophosphate decarboxylase, where the rapid (μs timescale) motion of a single loop dominates the transition between catalytically inactive and active conformations. In contrast, the (βα)8-barrels of tryptophan and histidine biosynthesis, such as the specialist isomerase enzymes HisA and TrpF, and the bifunctional isomerase PriA, are decorated by multiple long loops that undergo conformational transitions on the ms (or slower) timescale. Studying the interdependent motions of multiple slow loops, and their role in catalysis, poses a significant computational challenge. This work combines conventional and enhanced molecular dynamics simulations with empirical valence bond simulations to provide rich detail of the conformational behavior of the catalytic loops in HisA, PriA and TrpF, and the role of their plasticity in facilitating bifunctionality in PriA and evolved HisA variants. In addition, we demonstrate that, similar to other enzymes activated by ligand-gated conformational changes, loops 3 and 4 of HisA and PriA act as gripper loops, facilitating the isomerization of the large bulky substrate ProFAR, albeit now on much slower timescales. This hints at convergent evolution on these different (βα)8-barrel scaffolds. Finally, our work highlights the potential of engineering loop dynamics as a powerful tool to artificially manipulate the diverse catalytic repertoire of TIM-barrel proteins.
Leicht abspaltbare Schutzgruppen für die Säureamidfunktion, 3. Derivate des Asparagins und Glutamins mit 2.4‐dimethoxy‐benzyl‐und 2.4.6‐trimethoxy‐benzyl‐geschützten Amidgruppen (1968)

Abstract Die Synthese verschiedener für Peptidsynthesen geeigneter Derivate des Asparagins und Glutamins mit 2.4‐dimethoxy‐benzyl‐ und 2.4.6‐trimethoxy‐benzyl‐geschützten Amidgruppen wird beschrieben. Damit durchgeführte Synthesen einfacher Peptide verlaufen ohne Nebenreaktionen.
Surgical Treatment of Tarsal Coalitions (1994)

Twenty-nine patients with 39 tarsal coalitions were evaluated 1–10 years (average 3 years) after surgical treatment. Calcaneonavicular coalitions without secondary radiologic tarsal changes were scored as excellent or good results after excision and muscle interposition. Patients with secondary changes had slower rehabilitation, a higher recurrence rate, and a less favorable end result. Excision of talocalcaneal coalitions can provide good results, although, they are less predictable than calcaneonavicular coalitions. Most patients with a talocalcaneal coalition treated by excision and arthroeresis with a sinus tarsi spacer showed unsatisfactory early results because of severe tarsal pain. Long-term results after removal of the painful spacers were slightly better than those of patients not treated with spacers.
Upon the Shoulders of Giants: Open-Source Hardware and Software in Analytical Chemistry (2017)

Isaac Newton famously observed that "if I have seen further it is by standing on the shoulders of giants." We propose that this sentiment is a powerful motivation for the "open-source" movement in scientific research, in which creators provide everything needed to replicate a given project online, as well as providing explicit permission for users to use, improve, and share it with others. Here, we write to introduce analytical chemists who are new to the open-source movement to best practices and concepts in this area and to survey the state of open-source research in analytical chemistry. We conclude by considering two examples of open-source projects from our own research group, with the hope that a description of the process, motivations, and results will provide a convincing argument about the benefits that this movement brings to both creators and users.
Foldable Cylinder, the Potential Concept for Actuators and Bellows (2011)

This paper presents a new concept of actuators and bellows based on the rigid foldable cylinder discovered recently. Connelly et al proved that when a concave polyhedron is deformed, its volume remains constant in 1997. In spite of this rigorous mathematical theory, we have observed a real model of rigid polyhedral cylinder which changed volume substantially at some particular situation. Inspired with this phenomenon, we have identified that particular situation where the model, made of practical engineering material, can change its volume. This phenomenon is now applied to propose the new concept for actuators and bellows.
Advances in Internet and interconnectivity of networks (2002)

Internet has traditionally been an educational and research oriented network with global access. In modern times, with computer communications being practical, Internet offers an interconnecting medium for data, information, and file transfer. In addition, services and tools are being continuously added to the Internet and the network operation is being constantly upgraded and made more and more reliable. Internet has been steadily expanding not only in academic and research circles, but also in the industrial and commercial areas. For example, it is a simple matter of conversing with another user on the Internet for immediate exchange of information in banking and other financial operations. In addition, considerable effort is being spent to make the Internet more interactive for integrated voice and data services. From a system point of view Internet provides end to end digital connectivity. Also, being a driven network at the higher layers, Internet tends to be more fault than the original architecture. The advances in Internet, and associated applications are summarised.
The History of Local Government in England, being a re-issue of Book I of Local Government in England. By Redlich Josef and W. Hirst Francis. Edited with Introduction and Epilogue by Keith-Lucas Brian, Fellow of Nuffield College and Senior Lecturer in Local Government in the University of Oxford. [London: Macmillan & Co., Ltd.1958. xv and 256 and (index) 3 pp. 30s. net.] (1959)

The History of Local Government in England, being a re-issue of Book I of Local Government in England. By Redlich Josef and W. Hirst Francis. Edited with Introduction and Epilogue by Keith-Lucas Brian, Fellow of Nuffield College and Senior Lecturer in Local Government in the University of Oxford. [London: Macmillan &amp; Co., Ltd.1958. xv and 256 and (index) 3 pp. 30s. net.] - Volume 17 Issue 1
All-optical hash code generation and verification for low latency communications (2013)

We introduce an all-optical, format transparent hash code generator and a hash comparator for data packets verification with low latency at high baudrate. The device is reconfigurable and able to generate hash codes based on arbitrary functions and perform the comparison directly in the optical domain. Hash codes are calculated with custom interferometric circuits implemented with a Fourier domain optical processor. A novel nonlinear scheme featuring multiple four-wave mixing processes in a single waveguide is implemented for simultaneous phase and amplitude comparison of the hash codes before and after transmission. We demonstrate the technique with single polarisation BPSK and QPSK signals up to a data rate of 80 Gb/s.
Analysis of phone confusion matrices in a manually annotated French-German learner corpus (2016)

This paper presents an analysis of the non-native and native pronunciations observed in a phonetically annotated bilingual French-German corpus. After a forced-choice automatic annotation a large part of the corpus was checked and corrected manually on the phone level which allows a detailed comparison of the realized sounds with the expected sounds. The analysis is reported in terms of phone confusion matrices for selected error-prone classes of sounds. It revealed that German learners of French have most problems with obstruents in word-final position whereas French learners of German show complex interferences with the vowel contrasts for length and quality. Finally, the correct pronunciation rate of the sounds, for several phonetic classes, is analyzed with respect to the learner’s level, and compared to native pronunciations. One outcome is that different sound classes show different correct rates over the proficiency levels. For the German data the frequently occurring syllabic [=n] is a prime indicator of the proficiency level. Index Terms: Language learning, speech corpus, pronunciation variants, non-native speech 1.
Significances of Cathepsin B in Tumor Molecular Targeted Therapy (2012)

Cathepsin B is a cysteine protease,with close relevance to tumor progression,which is over-expressed in several malignant tumors.Cathepsin B plays an important role in molecular targeted therapy.This paper reviewed the latest developments of its biological characteristics,endogenous and exogenous inhibitors and Cathepsin B-based prodrugs.
A Peptide Prodrug Approach for Improving Bisphosphonate Oral Absorption (2000)

This work was aimed at improving the absorption of bisphosphonates by targeting carrier systems in the intestine and the intestinal peptide carrier system (hPEPT1), in particular. (14)C-Labeled pamidronate and alendronate as well as radiolabeled and "cold" peptidyl-bisphosphonates, Pro-[(3)H]Phe-[(14)C]pamidronate, and Pro-[(3)H]Phe-[(14)C]alendronate were synthesized. In situ single-pass perfusion studies revealed competitive inhibition of transport by Pro-Phe, suggesting peptide carrier-mediated transport. Prodrug transport in the Caco-2 cell line was significantly better than that of the parent drugs, and the prodrugs exhibited high affinity to the intestinal tissue. Oral administration of the dipeptidyl prodrugs resulted in a 3-fold increase in drug absorption following oral administration in rats, and the bioavailability of Pro-Phe-alendronate was 3.3 (F(TIBIA)) and 1.9 (F(URINE)) times higher than that of the parent drug. The results indicate that the oral absorption of bisphosphonates can be improved by peptidyl prodrugs via the hPEPT1; however, other transporters may also be involved.
Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals (2017)

Taken together, the main finding on this report suggests that association between increased BMI and accelerated epigenetic aging in the blood cells of middle-aged individuals can be observed, and this effect is also detectable if the BMI has increased in adulthood. The fact that the association between BMI and epigenetic age can only be observed in the middle-aged group does not exclude the possibility that this association could be present throughout the human lifespan; it might just be masked by confounding factors in young adults and nonagenarian individuals.
Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity (2020)

Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes hallmark debilitating polyarthralgia, fever, and rash in patients. T cell-mediated immunity, especially CD4<sup>+</sup> T cells, are known to participate in the pathogenic role of CHIKV immunopathology. The other T cell subsets, notably CD8<sup>+</sup>, NKT, and gamma-delta (γδ) T cells, can also contribute to protective immunity, but their effect is not actuated during the natural course of infection. This review serves to consolidate and discuss the multifaceted roles of these T cell subsets during acute and chronic phases of CHIKV infection, and highlight gaps in the current literature. Importantly, the unique characteristics of skin-resident memory T cells are outlined to propose novel prophylactic strategies that utilize their properties to provide adequate, lasting protection.
Requirement of the JIP1 scaffold protein for stress-induced JNK activation (2001)

The c-Jun N-terminal kinase (JNK) signal transduction pathway is activated in response to the exposure of cells to environmental stress. Components of the JNK signaling pathway interact with the JIP1 scaffold protein. JIP1 is located in the neurites of primary hippocampal neurons. However, in response to stress, JIP1 accumulates in the soma together with activated JNK and phosphorylated c-Jun. Disruption of the Jip1 gene in mice by homologous recombination prevented JNK activation caused by exposure to excitotoxic stress and anoxic stress in vivo and in vitro. These data show that the JIP1 scaffold protein is a critical component of a MAP-kinase signal transduction pathway.
A downward counter-factual climate risk analysis of the impact of tropical cyclones in the Caribbean islands (2020)

&amp;lt;p&amp;gt;Climate risk analysis and assessment studies are typically conducted relying on historical data. These data, however, represent just one single realization of the past, which could have unfolded differently. As an example, Hurricane Irma might had struck South Florida at Category 4 and, had it done so, damages could have been as high as 150 billion, about three times higher than damage estimated from the actual event. To explore the impacts of these potentially catastrophic near-misses, downward counter-factual risk analysis (Woo, Maynard and Seria, 2017) complements standard risk analysis by exploring alternative, plausible realization of past climatic events. As downward counter-factual risk analysis frames risk in an event-oriented manner, corresponding more closely to how people perceive risk, it is expected to increase climate risk awareness among people and policy makers (Shepherd et al., 2018).&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;We present a counter-factual risk analysis study of climate risk from tropical cyclones on the Caribbean islands. The analysis is conducted using the natcat impact model CLIMADA (Aznar-Siguan and Bresch, 2019). Impact is estimated based on forecasts of past tropical cyclones tracks from the THORPEX Interactive Grand Global Ensemble (TIGGE) dataset, as they all represent plausible alternative realizations of past tropical cyclones. The goal is to study whether, and to what extent, the estimated impacts from forecasts provide new insights than those provided by historical records in terms of e.g. cumulated annual damages, maximum annual damages and, in so doing, perform a worst-case analysis study to support climate risk management planning.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;lt;br&amp;gt;Aznar-Siguan, G. and Bresch, D. N.: CLIMADA v1: a global weather and climate risk assessment platform, Geosci. Model Dev., 12, 3085-3097, doi.org/10.5194/gmd-12-3085-2019, 2019.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Woo, G., Maynard, T., and Seria, J. Reimagining history. Counterfactual risk analysis. Retrieved from: https://www.lloyds.com/~/media/files/news-and-insight/risk-insight/2017/reimagining-history.pdf, 2017.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Shepherd, T.G., Boyd, E., Calel, R.A. et al.: Storylines: an alternative approach to representing uncertainty in physical aspects of climate change. Climatic Change 151, 555&amp;amp;#8211;571, doi.org/10.1007/s10584-018-2317-9 , 2018.&amp;lt;/p&amp;gt;
Importance of Diarrhea in Evaluating Constipation in Irritable Bowel Syndrome Clinical Studies (2011)

IBS patients' self-assessment of constipation and diarrhea severity using the C-D score is an effective predictor of C-IBS and constipation severity. The C-D score may be a useful tool in future IBS constipation trials, as it seems to predict constipation and it correlates well with stool diaries.
Interfacial Biomimetic Synthesis of Silica Nanocapsules Using a Recombinant Catalytic Modular Protein (2015)

This paper reports interfacially driven synthesis of oil-core silica-shell nanocapsules using a rationally designed recombinant catalytic modular protein (ReCaMoP), in lieu of a conventional chemical surfactant. A 116-residue protein, D4S2, was designed by modularizing a surface-active protein module having four-helix bundle structure in bulk and a biosilicification-active peptide module rich in cationic residues. This modular combination design allowed the protein to be produced via the industrially relevant cell factory Escherichia coli with simplified purification conferred by thermostability engineered in design. Dynamic interfacial tension and thin film pressure balance were used to gain an overview of the protein behavior at macroscopic interfaces. Functionalities of D4S2 to make silica nanocapsules were demonstrated by facilitating formation and stabilization of pharmaceutically grade oil droplets through its surface-active module and then by directing nucleation and growth of a silica shell at the oil–water interface through its biosilicification-active module. Through these synergistic activities in D4S2, silica nanocapsules could be formed at near-neutral pH and ambient temperature without using any organic solvents that might have negative environmental and sustainability impacts. This work introduces parallelization of biomolecular, scale-up and interfacial catalytic design strategies for the ultimate development of sustainable and scalable production of a recombinant modular protein that is able to catalyze synthesis of oil-filled silica nanocapsules under environmentally friendly conditions, suitable for use as controlled-release nanocarriers of various actives in biomedical and agricultural applications.
Mechanical Responses of Silicon Nitrides Under Dynamic Endentation (2008)

Mechanical responses of five silicon nitrides have been experimentally studied by using dynamic and standard hardness tests. The indentation loads ranged from several newtons to several hundred newtons. In the dynamic test, a load pulse with ∼ 100 μs rise time was achieved. Indentation size effect (ISE) and loading rate effects on the Vickers hardness were observed for the silicon nitrides. The ISE was further characterized by using the Meyer law and the energy-balance or proportional specimen resistance (PSR) model. The conventional brittleness approach is not satisfactory in characterizing transition between plasticity and fracture, and a new brittleness concept is proposed based on the PSR model that appears to capture the dynamic indentation responses of the materials.
Chemokine CCL2 facilitates ICAM‐1‐mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes (2008)

We examined the effects of CCL1, CCL2, CCL12 and CCL21 on the expression of adhesion molecules in cultured human lymphatic endothelial cells using immunohistochemical staining or Western blot analysis. In addition, we investigated whether the expressed adhesion molecule was able to facilitate the attachment of carcinoma cells to the lymphatic endothelial cells as an in vitro micrometastatic model. CCL2 caused a selective and significant expression of ICAM-1 on human lymphatic endothelial cells but CCL1, CCL12 and CCL21 did not. By increasing the stimulation time from 4 to 18 and 48 h, the intensity of immunoreactivity for ICAM-1 was significantly increased in a time-dependent manner up to 18 h. The ICAM-1 mRNA levels were also elevated significantly up to 18 h. The CCL2-mediated immunohistochemical expression of ICAM-1 was dose-dependently increased from 10 pg/mL to 1 ng/mL. The CCL2-mediated expression of ICAM-1 was significantly reduced by neutralization of CCL2 using a specific CCL2 antibody. The 18-h treatment with CCL2 caused a significant facilitation of in vitro attachment of MDA-MB-231 and MCF-7 cells to the lymphatic endothelial cells (LECs). The CCL2-mediated response in the attachment assay was also significantly reduced either by the neutralization of CCL2 or by additional treatment with anti-ICAM-1 antibody. Immunohistochemical expression of ICAM-1, but not E-selectin, was strongly observed around and within the metastatic region of sentinel lymph node isolated from breast cancer patients. These findings suggest that CCL2 induces selective and significant expression of ICAM-1 on cultured human lymphatic endothelial cells and then facilitates the attachment of carcinoma cells to the lymphatic endothelial cells, thus providing an in vitro micrometastatic model via the overexpression of ICAM-1.
Influence of nutrition therapy on the intestinal microbiome (2016)

Focus of research is shifting toward strategies that augment the intestinal environment to facilitate growth of beneficial microorganisms, strengthen colonization resistance, and maintain immune homeostasis.
Chiral Bis(oxazoline) Copper(II) Complexes:  Versatile Catalysts for Enantioselective Cycloaddition, Aldol, Michael, and Carbonyl Ene Reactions (2000)

A bis(oxazoline) (box) copper(II) complex and its hydrated counterpart (1 and 2) function as enantioselective Lewis acid catalysts for carbocyclic and hetero Diels-Alder, aldol, Michael, ene, and amination reactions with substrates capable of chelation through six- and five-membered rings. X-ray crystallography of the chiral complexes reveals a propensity for the formation of distorted square planar or square pyramidal geometries. The sense of asymmetric induction is identical for all the processes catalyzed by [Cu((S,S)-t-Bu-box)](X)(2) complexes 1 and 2 (X = OTf and SbF) resulting from the intervention of a distorted square planar catalyst-substrate binary complex. These catalyzed processes exhibit excellent temperature-selectivity profiles. Reactions catalyzed by [Cu(S,S-Ph-pybox)](SbF(6))(2) and their derived chelation complexes are also discussed.
Dose-Response Study of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children (2005)

One injection of high potency MMRV resulted in antibody responses to the 4 vaccine components equivalent to those found after concomitant administration of M-M-RII and VARIVAX. A second injection of MMRV resulted in a significant boost in VZV antibody. This boost may translate into enhanced immunogenicity against varicella, which is known to correlate with increased protection.
Multiple pathways of propranolol's metabolism are inhibited by debrisoquin (1989)

We investigated the effect of debrisoquin on propranolol metabolism in six normal subjects who were extensive metabolizers of debrisoquin. Each subject was studied on two occasions. On the first occasion, each subject received oral propranolol (80 mg) alone; on the second occasion, 7 days later, each subject received a dose of propranolol (80 mg) 30 minutes after the administration of oral debrisoquin (40 mg). Oral propranolol clearance was reduced 33% +/- 16% (p less than 0.05) by the administration of debrisoquin. As predicted, the 4-hydroxypropranolol partial metabolic clearance was significantly (p less than 0.05) inhibited by debrisoquin. However, the side-chain oxidation pathway, as measured by naphthoxylactic acid, was also significantly (p less than 0.05) inhibited by debrisoquin. Debrisoquin administration did not change the renal clearance of any of the metabolites. These data support the usefulness of the in vivo inhibition model in the prediction of cosegregation of routes of metabolism. However, for propranolol, pathways of its metabolism that are not thought to cosegregate with debrisoquin was also inhibited.