gebhart/patrepeval huggingface dataset:
Pteridines. Part CXVIII (2007)

Abstract Our approach to achieve a partial synthesis of methanopterin ( 1 ) started from 6‐acetyl‐ O 4 ‐isopropyl‐7‐methylpterin ( 20 ) which was obtained either by condensation from 6‐isopropoxypyrimidine‐2,4,5‐triamine ( 19 ) and pentane‐2,3,4‐trione ( 6 ) or from 6‐isopropoxy‐5‐nitrosopyrimidine‐2,4‐diamine ( 21 ) and pentane‐2,4‐dione (=acetylacetone; 22 ) ( Scheme 2 ). NaBH 4 reduction of 20 led to 6‐(1‐hydroxyethyl)‐ O 4 ‐isopropyl‐7‐methylpterin ( 23 ) which was converted into the corresponding 6‐(1‐chloroethyl) and 6‐(1‐bromoethyl) derivatives 24 and 25 . A series of nucleophilic displacement reactions in the side chain and at position 4 were performed as model reactions to give 26 – 29, 32 – 35 , and 39 – 41 . Hydrolysis of the substituents at C(4) led to the corresponding pterin derivatives 30, 31, 36 – 38 , and 42 . Analogously, 25 reacted with 1‐(4‐aminophenyl)‐1‐deoxy‐2,3: 4,5‐di‐ O ‐isopropylidene‐ D ‐ribitol ( 43 ), prepared from N ‐(4‐bromophenyl)benzamide ( 47 ) via 49 and 50 to give 1‐{4‐{{1‐[2‐amino‐7‐methyl‐4‐(1‐methylethoxy)pteridin‐6‐yl]ethyl}amino}phenyl}‐1‐deoxy‐ D ‐ribitol ( 44 ) in 62% yield ( Scheme 3 ). Acid cleavage of the isopropylidene groups at room temperature led to 45 and on boiling to 1‐{4‐{[1‐(2‐amino‐3,4‐dihydro‐7‐methyl‐4‐oxopteridin‐6‐yl)ethyl]amino}phenyl}‐1‐deoxy‐ D ‐ribitol ( 46 ). The next step, however, attachment of the ribofuranosyl moiety with 55 or 56 to the terminal 1‐deoxy‐ D ‐ribitol OH group could not been achieved. The second component, bis(4‐nitrobenzyl) 2‐{[(2‐cyanoethoxy)(diisopropylamino)phosphino]oxy}pentanedioate ( 61 ), to built‐up methanopterin ( 1 ) was synthesized from 2‐hydroxypentanedioic acid ( 59 ) and worked well in another model reaction on phosphitylation with N 6 ‐benzoyl‐2′,3′‐ O ‐isopropylideneadenosine and oxidation to give 62 ( Scheme 6 ).
X-Ray Based Subpicosecond Electron Bunch Characterization Using 90° Thomson Scattering (1996)

X rays produced by 90\ifmmode^\circ\else\textdegree\fi{} Thomson scattering of a femtosecond, near infrared, terawatt laser pulse of a 50 MeV electron beam are shown to be an effective diagnostic to measure transverse and longitudinal density distributions of an electron beam ( $e$ beam) with subpicosecond time resolution. The laser beam was focused onto the $e$-beam waist, generating 30 keV x rays in the forward direction. The transverse and longitudinal $e$-beam structures have been obtained by measuring the intensity of the x-ray beam, while scanning the laser beam across the $e$ beam in space and time. The $e$-beam divergence has been obtained through measurement of spatial and spectral characteristics of the scattered x-ray beam.
Wnt5a induces ROR1 to recruit DOCK2 to activate Rac1/2 in chronic lymphocytic leukemia (2018)

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic protein expressed on chronic lymphocytic leukemia (CLL) that can serve as a receptor for Wnt5a, which can promote leukemia cell migration, proliferation, and survival. We found Wnt5a could induce ROR1 to complex with DOCK2 (dedicator of cytokinesis 2) and induce activation of Rac1/2; these effects could be blocked by cirmtuzumab, a humanized anti-ROR1 monoclonal antibody. We find that silencing DOCK2 specifically impaired the capacity of Wnt5a to induce activation of Rac1/2 or enhance CLL cell proliferation. We generated truncated forms of ROR1 and found the cytoplasmic proline-rich domain (PRD) of ROR1 was required for Wnt5a to induce ROR1 to complex with DOCK2 and activate Rac1/2 in the CLL cell-line MEC1. We introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1-PRD at potential binding sites for the Src-homology 3 domain of DOCK2. In contrast to wild-type ROR1, or other ROR1 P→A variants, ROR1<sup>P808A</sup> was unable to recruit DOCK2 in response to Wnt5a. Moreover, unlike MEC1 cells transfected with wild-type ROR1 or ROR1 with P→A substitutions at positions 784, 826, or 841, MEC1 cells transfected to express ROR1<sup>P808A</sup> did not have a growth advantage over MEC1 cells that do not express ROR1. This study reveals that the recruitment of DOCK2 may be critical for the capacity of Wnt5a to enhance CLL proliferation, which may contribute to the observed increased tendency for disease progression in patients who have CLL cells that express high levels of ROR1.
Mucin 5B, carbonic anhydrase 9 and claudin 18 are potential theranostic markers of gallbladder carcinoma (2018)

CLDN18 is a new metaplasia marker in gallbladder tissues, and is conserved in approximately half of GBC cases. MUC5B and CA9 are highly conserved during GBC histological progression. The three markers are potential theranostic markers, in particular CA9 and CLDN18, for which there are already targeted therapies available.
Scattering experiments on polymer solutions (1993)

Abstract Laser light‐scattering characterization of poly(tetrafluoroethylene) (PTFE) in a perfluoroalkane (perfluorotetracosane) or oligomers of poly(chlorotrifluoroethylene) at temperatures near the crystalline melting point of PTFE and studies of the coil‐to‐globule transition for polystyrene in cyclohexane are reviewed. Discussions on approach to solving some experimental problems are emphasized. © 1993 John Wiley &amp; Sons, Inc.
P4‐143: LOSS OF PDE4D REGULATION OF CAMP‐PKA‐CALCIUM SIGNALING IN THE AGING ASSOCIATION CORTEX: INCREASING RISK FOR LOAD (2019)

Tau pathology in late-onset Alzheimer's disease (LOAD) targets the glutamatergic neurons in the association cortices, including the newly evolved dorsolateral prefrontal cortex (dlPFC). Our recent data revealed that aging rhesus macaques can be used to study LOAD pathology, as they recapitulate the qualitative pattern and sequence of tau pathology seen in humans, including neurofibrillary tangles and signs of increased cAMP-PKA-calcium signaling in tau-afflicted circuits. cAMP-PKA-calcium signaling becomes dysregulated in the aging dlPFC due to loss of phosphodiesterase (PDE4) activity, likely via elevated MK2-mediated neuroinflammation, contributing to cognitive impairment and PKA-phosphorylation at pS214Tau and pS2808RyR2. pS214Tau is an important intermediate that causes tau to detach from microtubules and aggregate, and pS2808RyR2 induces greater calcium “leak” from ryanodine receptors into the cytosol. Previous research focused on the PDE4A isozyme, but PDE4D is of great interest, since it is the predominant isoform and decreased in aged human dlPFC. However, the localization of PDE4D in dlPFC neurons is unknown, and whether it interacts with organelles associated with tau pathology, calcium dysfunction and neuroinflammation. Using high-spatial resolution immunoelectron (immunoEM) microscopy, we interrogated the subcellular localization of PDE4D in young and aged dlPFC. The anatomical distribution of PDE4D in young dlPFC was compared to the distribution of pS214Tau, pS2808RyR2 and MK2 in aged dlPFC. The ultrastructural localization of PDE4D in the young dlPFC was similar to the locations where pS214Tau, pS2808RyR2 and MK2 collects in the aged dlPFC. PDE4D was especially prominent in dendrites near microtubules and the smooth endoplasmic reticulum (SER), in close proximity to mitochondria. There was also significant postsynaptic labeling in dendritic spines, in association with the SER spine apparatus near glutamate-like axospinous synapses. In aged dlPFC, PDE4D was completely lost from postsynaptic locations, but remained in glia. Ultrastructural results suggest PDE4D is critically positioned in dlPFC glutamatergic microcircuits to modulate cAMP-PKA-calcium signaling. Loss of PDE4D expression with advancing age may render association cortices particularly susceptible to cAMP dysregulation of internal calcium release via RyR2, and cAMP-PKA phosphorylation of tau and risk of LOAD. These events in the aging cortex may provide an opportunity for therapeutic intervention at early stages of disease.
Granulocyte colony‐stimulating factor has a negative effect on stroke outcome in a murine model (2007)

The administration of CD34-positive cells after stroke has been shown to have a beneficial effect on functional recovery by accelerating angiogenesis and neurogenesis in rodent models. Granulocyte colony-stimulating factor (G-CSF) is known to mobilize CD34-positive cells from bone marrow and has displayed neuroprotective properties after transient ischemic stress. This led us to investigate the effects of G-CSF administration after stroke in mouse. We utilized permanent ligation of the M1 distal portion of the left middle cerebral artery to develop a reproducible focal cerebral ischemia model in CB-17 mice. Animals treated with G-CSF displayed cortical atrophy and impaired behavioral function compared with controls. The negative effect of G-CSF on outcome was associated with G-CSF induction of an exaggerated inflammatory response, based on infiltration of the peri-infarction area with CD11b-positive and F4/80-positive cells. Although clinical trials with G-CSF have been started for the treatment of myocardial and limb ischemia, our results indicate that caution should be exercised in applying these results to cerebral ischemia.
Preliminary Results of Bioactive Amniotic Suspension with Allograft for Achieving One and Two-Level Lumbar Interbody Fusion (2016)

Fusion status is evaluated with many different biologics and varying methods in the literature. BAS with allograft in this study demonstrated high fusion rates with no complications within a largely comorbid population. Although a small population, BAS with allograft results were encouraging for one and two-level lumbar interbody fusion in this study. Further prospective studies should be conducted to investigate safety and efficacy in a larger population.
Organic multishell isostructural host–guest crystals: fullerenes C60 inside a nitroxide open framework (2013)

The dinitroxide biradical crystallizes forming hexagonal open frameworks with one-dimensional corrugated channels filled with crystallization solvent. The large pockets constitutive of the channels allowed the inclusion of C(60) in the paramagnetic network. The rapidity and high fidelity of crystal growth were used to prepare isostructural multilayer host-guest crystals successively stained with C(60).
Modifying the Energy Levels in Phenoxazine Based Sensitizers for Dye Sensitized Solar Cells (2011)

This thesis gives a detailed description of the design and synthesis of new organic sensitizers for Dye sensitized Solar Cells (DSCs). It is divided in 7 chapters, where the first gives an introduction to the field of DSCs and the synthesis of organic sensitizers. Chapters 2 to 6 deal with the work of the author, starting with the first publication and the other following in chronological order. The thesis is completed with some concluding remarks (chapter 7). The DSC is a fairly new solar cell concept, also known as the Gratzel cell, after its inventor Michael Gratzel. It uses a dye (sensitizer) to capture the incident light. The dye is chemically connected to a porous layer of a wide band-gap semiconductor. The separation of light absorption and charge separation is different from the conventional Si-based solar cells. Therefore, it does not require the very high purity materials necessary for the Si-solar cells. This opens up the possibility of easier manufacturing for future large scale production. Since the groundbreaking work reported in 1991, the interest within the field has grown rapidly. Large companies have taken up their own research and new companies have started with their focus on the DSC. So far the highest solar energy to electricity conversion efficiencies have reached ~12%. The sensitizers in this thesis are based on triphenylamine or phenoxazine as the electron donating part in the molecule. A conjugated linker allows the electrons to flow from the donor to the acceptor, which will enable the electrons to inject into the semiconductor once they are excited. Changing the structure by introducing substituents, extending the conjugation and exchanging parts of the molecule, will influence the performance of the solar cell. By analyzing the performance, one can evaluate the importance of each component in the structure and thereby gain more insight into the complex nature of the dye sensitized solar cell.
Detection of Novel Visible-Light Region Absorbance Peaks in the Urine after Alkalization in Patients with Alkaptonuria (2014)

We found two characteristic peaks at 406 nm and 430 nm in both alkaptonuric urine and HGA solution after alkalization. This new quick and easy method may pave the way for the development of an easy method for the diagnosis of alkaptonuria.
Estimation of Folding Probabilities and Φ Values From Molecular Dynamics Simulations of Reversible Peptide Folding (2006)

Molecular dynamics simulations with an implicit model of the solvent have allowed to investigate the reversible folding of structured peptides. For a 20-residue antiparallel beta-sheet peptide, the simulation results have revealed multiple folding pathways. Moreover, the conformational heterogeneity of the denatured state has been shown to originate from high enthalpy, high entropy basins with fluctuating non-native secondary structure, as well as low enthalpy, low entropy traps. An efficient and simple approach to estimate folding probabilities from molecular dynamics simulations has allowed to isolate conformations in the transition state ensemble and to evaluate Phi values, i.e., the effects of mutations on the folding kinetics and thermodynamic stability. These molecular dynamics studies have provided evidence that, if interpreted by neglecting the non-native interactions, Phi values overestimate the amount of native-like structure in the transition state.
A new oxindole synthesis (1991)

A quaternary carbon atom can be set up by irradiation of the N-methylaniline enamine 5 of adamantane-2-carbaldehyde giving the indoline 6 in poor yield. This product was converted into the spiro-oxindole 8, but only in very low yield. Quaternary carbon atoms can be set up more efficiently from the ketone group of adamantanone in two high-yielding steps by conjugate addition of appropriate organometallic carbon nucleophiles to the electrophilic alkenes 9 and 25, obtained by condensation of adamantanone with either Meldrum's acid or nitromethane. By use of the latter intermediate 25, a high yielding, eight-step conversion of adamantanone into the corresponding spiro-oxindole 8 can be carried out. Conjugate addition of triphenylaluminium to the corresponding nitroalkene 33 derived from 2-oxaadamantan-4-one 32 takes place with high stereoselectivity in the sense appropriate for a synthesis of gelsemine, with the phenyl group in the product 34cis to the oxygen bridge.
X-ray optics R&amp;D at NSLSII: focus on optical metrology development (2016)

The push for high quality x-ray optics is closely linked to improvements in metrology technology. During the last decade, we have seen an ultra-fast progress in x-ray optics performances. This enhancement is directly linked to the development of the necessary tools to control these optical components. These metrology tools are necessary for the fabrication (to guide some polishing deterministic process) and also for the ultimate characterization used to validate surface parameters (often inside their own mechanical support) prior to installation in a beam line. It is now necessary to characterize optical surface figure, slope errors and roughness on meter-long optics over spatial frequencies as short as 0.1 mm and with slope errors reaching less than 100 nrad rms or surface figure errors close to 1 nm in order to not spoiled and preserve the high brightness made available by third and fourth generation synchrotron/FEL sources like NSLSII or LCLS. For this purpose, the new NSLS-II Optical Metrology Laboratory (NSLSII-OML) includes commercial instruments for measuring long spatial frequency figure errors, mid spatial frequencies and high frequency roughness and had started some research and development activities. This paper provides a brief description of the instruments currently available in the laboratory and gives an overview of the very active research and development efforts within the NSLSII-OML.
Ein Michelin-Federungssystem, das den Reifenkontaktbereich durch negativen Radsturz optimiert (2001)

Das Ziel der Reifenkonstrukteure besteht darin, die Reifenleistung im Hinblick auf die Optimierung der Gesamtleistung des Fahrzeugs kontinuierlich zu verbessern. Michelin-Ingenieure fuehrten Arbeiten an durch, um deren ideale Betriebsbedingungen bestimmen zu koennen. Dieser Ansatz fuehrte zur Untersuchung einer innovativen Weiterentwicklung des gegenwaertigen Federungssystems und zur Vorstellung vom System des optimierten Kontaktbereichs. Dieses System des optimierten Kontaktbereichs ist ein passives System, das einen negativen Radsturz liefert, der im direkten Zusammenhang zu der Seitenkraft steht, die vom beim Kurvenfahren abgegeben wird. ABSTRACT IN ENGLISH: The tire engineer's aim is to continuously improve tire performance, with a view to optimising vehicle overall performance. Work on tires has been conducted by Michelin engineers to determine their ideal operating conditions. This approach led them to investigate an innovative development of current suspension systems and to imagine the Optimised Contact Patch System. This Optimised Contact Patch System is a passive system which provides a negative camber directly linked to the lateral force supplied by the tire when cornering. Some of the vehicle performance largely depends on the tyre's performance which is related not only to its own design (architecture, materials, etc.), but also to the operating conditions (temperature, positioning on the ground, etc.). Optimal conditions for tire operation and related performance can thus be determined independently from technical limitations of state-of-the-art suspension systems. (A) Beitrag zum Themenbereich Systemintegration der Tagung Reifen Fahrwerk Fahrbahn der VDI-Gesellschaft Fahrzeug- und Verkehrstechnik, Hannover, 18. und 19. Oktober 2001.
Clinical Utility of Emerging Molecular Diagnostics in Breast Cancer (2016)

Molecular diagnostic tests are increasingly used in the clinic to tailor therapy to the molecular characteristics of a cancer. In early stage estrogen receptor (ER)-positive cancer, the 21-gene recurrence score assay, as well as other gene expression signature-based tests are routinely used to assist in identifying patients for adjuvant chemotherapy. A new generation of tests has also been developed for ER-positive cancers to estimate the risk of late recurrence and benefit from extended adjuvant endocrine therapy and therefore identify patients who require 10 years of endocrine therapy. Among triple-negative breast cancers (TNBC), there is increasing evidence that patients with germline BRCA mutant cancers are highly sensitive to platinum drugs, and inclusion of this agent with an anthracycline- and taxane-based regimen might improve their outcome. Other proposed “BRCA-ness” markers are also being tested in the clinic. Extensive immune cell infiltration (lymphocyte predominant breast cancer) that can be detected by counting tumor-infiltrating lymphocytes or measuring immune-specific gene expressions is an increasingly recognized favorable prognostic marker that also predicts greater chemotherapy sensitivity in TNBC and high-risk, ER-positive cancers. The clinical utility of immune markers is yet to be defined, but their importance will likely grow as immunotherapies are entering the clinic. In HER2-positive cancer, several markers demonstrated statistically significant associations with response to HER2-targeted therapies, but their predictive values to select one therapy over another or to omit HER2-targeted therapies are modest and have little clinical utility. Molecular target profiling of metastatic cancers is increasingly performed to determine clinical trial eligibility for targeted drugs and to identify potentially druggable alterations. Anecdotal examples demonstrate benefit from off-label use of targeted therapies in some patients with a matching molecular abnormality, but the clinical utility of this strategy is still under study in several ongoing clinical trials.
A deletion mutation in bovine SLC4A2 is associated with osteopetrosis in Red Angus cattle (2010)

These results indicate that a deletion mutation within bovine SLC4A2 is associated with osteopetrosis in Red Angus cattle. Loss of SLC4A2 function appears to induce premature cell death, and likely results in cytoplasmic alkalinization of osteoclasts which, in turn, may disrupt acidification of resorption lacunae.
Bacterial respiration keeps amazing us in the 21st century (2021)

The last two decades have seen some remarkable discoveries in bacterial bioenergetics. In this article, we highlight how important societal issues such as antimicrobial resistance and sustainable fuel production have led to a renewed focus on the bioenergetics of bacteria, which is only beginning to show us how much we have left to learn. Advances in technology, particularly through biophysics, have further contributed to a rapid progress in our understanding of the respiratory chain complexes in bacteria. Blue-sky research has seamlessly merged with solutions to societal problems and we stand on the precipice of a number of exciting discoveries in this field.
Ray Transfer Matrix of Conically Refracting Crystal for Laser Cavity Analysis (2018)

In this work, we develop the formalism of ray transfer matrices for conically refracting crystals and apply it for calculation of the cavity mode in the laser cavity featuring conically refracting element.
Microscopic and microbiological investigations of Mississippian sylvite (2012)

Sylvite is a potassium chloride (KCl) mineral that was first discovered in 1832 in evaporite deposits in sedimentary basins of Mt. Vesuvius. Sylvite is colorless (grey or white) but it is often found in association with red deposits of halite and a variety of other minerals (e.g., hilgardite, volkovskite, trembathite and strontioginorite). We have conducted an Optical Microscopy and Microbiological study of freshly fractured interior material of core samples of Sylvite and Halite from the Penobsquis Mines of Kings County, New Brunswick. These samples are dated as Early Carboniferous period, and of Mississippian sub-period (Toumaisian stage 345-359 Myr) from the Upper Halite Member of the Windsor Group Evaporites. During this study, viable microorganisms were isolated in enrichment cultures that represent an ancient life of the deposits. Currently, in microbiology, there are several records of the isolation of viable bacterial cultures from the Permian salt crystals and oil. In this article, we present the preliminary results of the study of ancient anaerobic enrichment cultures isolated from Mississippian Sylvite and Halite samples. Therefore, this study extends by more than 50 million years the paleontological record of viable and culturable microorganisms preserved in ancient salt crystals.