gebhart/patrepeval huggingface dataset:
Scalable Process of Spiro(cyclopropane)oxazepane Pyridine Carboxylic Acid through Kulinkovich, Mitsunobu, and Pd-Catalyzed Intramolecular C–N Coupling (2022)

The oxazepane pyridine intermediate, an important fragment of active pharmaceutical ingredients, is of great interest in the pharmaceutical industry. In this manuscript, a scalable and economical process for the synthesis of a fused 2′,3′-dihydro-5’H-spiro[cyclopropane-1,4′-pyrido[3,2-b][1,4]oxazepine]-8′-carboxylic acid 1 on multikilogram scales is described. The synthesis features a streamlined isolation process from the Mitsunobu reaction by using one solvent system for a two-step process. Furthermore, a robust palladium-catalyzed intramolecular amination for the seven-membered heterocycle was developed. The reproducible reaction rate was established by adding the catalyst and ligand as solids without preparing the palladium complex under nitrogen. The residual palladium was effectively reduced by recrystallization of the carboxylic ester intermediate 2. The synthesis of key intermediate 5 was realized via the Kulinkovich reaction from readily available simple building blocks. The regulatory starting material compound 1 was isolated in a high-purity profile after saponification of the ester 2 with an overall yield of 70% over five steps.
Toward Super Temporal Resolution by Suppression of Mixing Effects of Electrons (2022)

The theoretical temporal resolution limit of silicon (Si) image sensors is 11.1 ps. The super temporal resolution (STR) is defined as a frame interval less than this limit. The temporal resolution of burst image sensors is significantly affected by “mixing” of signal electrons traveling from different starting positions. For example, the penetration depths of photons incident to a surface of a photodiode (PD) disperse exponentially, resulting in mixing of the photoelectrons from different depths at the other end, which causes a distribution of the arrival times. The temporal resolution is proportional to the standard deviation of the arrival time. Toward STR imaging, this article proposes measures to suppress various mixing phenomena during the travel of the signal electrons: 1) a germanium (Ge) PD for visible light to practically eliminate the effect of vertical mixing caused by the distribution of the penetration depth; 2) an inverted pyramid PD to efficiently suppress the horizontal mixing, keeping a 100% fill factor; 3) a standard column PD with negative potential on the vertical walls to squeeze the trajectory bundle of electrons falling on the guide gate on the front side; and 4) a resistive guide gate to linearize the potential profile to maximize the horizontal drift velocity to minimize the mixing together with the squeezed electron bundle.
Establishment of ES Cells Secreting Human Factor VIII for Hemophilia A-Targeted Cell Therapy. (2006)

Abstract Hemophilia A is an X-linked bleeding disorder resulting from abnormality in the coagulation factor VIII (FVIII) gene. Although bleeding episodes can be prevented or treated by intravenous injection of FVIII concentrates, there are some drawbacks such as necessity of frequent intravenous transfusion and high cost of FVIII concentrates. Lots of basic studies for gene therapy have been reported but clinical trials for hemophilia have been interrupted by significant safety concerns. Cell-based therapy may overcome the disadvantages, without impairing the advantages of gene therapy. Therefore, we have tried to use embryonic stem (ES) cells for production of FVIII protein. For the stable expression of FVIII, we established tet-hFVIII ES cells, which induce human (h) FVIII mRNA (F8) by doxycycline (Dox) exposure. Tet-hFVIII ES cells were cultured in the serum containing and/or serum free media and then FVIII activity (FVIII:C) and FVIII antigen (FVIII:Ag) were measured in the supernatant by APTT-based FVIII:C assay and ELISA, respectively. In the previous study, we demonstrated that ES cells could be differentiated with serum into cells with mesoderm potentials such as hematopoietic and vascular endothelial cells. Although mRNA of hFVIII was detected by Dox induction, neither FVIII:C nor FVIII:Ag was detected in the conditioned media in undifferentiated ES cells and differentiated cells with mesoderm potentials. Next we cultured tet-hFVIII ES cells using endoderm and hepatocyte differentiation condition in which differentiated ES cells express Foxa2 and albumin genes (Kubo et al. Development 2003), since FVIII is known to be produced in the liver. Both FVIII:C (3.7 mIU/ml/mg protein) and FVIII:Ag (0.3 ng/ml/mg protein) were detected in the conditioned media for hepatocyte differentiation. These data demonstrated that ES cells could produce and secrete the functional hFVIII protein in our system, when ES cells cultured in the hepatocyte condition. The level of FVIII:C and FVIII:Ag were increased twice by addition of von Willebrand factor (2.5 μg/ml) into the culture media. Furthermore, Dox enhanced the level of FVIII:C and FVIII:Ag dose-dependently. In conclusion, we confirmed secretion of hFVIII in endodermal differentiation culture system. This system may be applicable for cell-based therapy targeting to hemophilia A.
Snytheses of analgesics. Part XXXVII. An alternative synthesis of 1,2,3,4, 5, 6‐hexahydro‐8‐hydroxy‐2,6‐methano‐6, h‐dimethyl‐3‐phenethyl‐3‐benzazoeine [studies on the syntheses of heterocyclic compounds. Part DXXI] (1973)

Abstract Acid treatment of the alkylated products of (Va, Vb, and VIII) of piperidinols IVa and IVb, and tetrahydropyridine VII with β‐bromoethylbenzene, afforded 1,2,3,4,5,6‐hexahydro‐8‐hydroxy‐2,6‐methano‐6,1 1‐dimethyl‐3‐phenethyl‐3‐benzazocine (la) in good yield. Piperidinols Va and Vb were also obtained from the reaction of N ‐(3‐methyl‐3‐pentenyl)‐β‐phenethylamine (IIb) with methyl 3‐(4‐methoxyphenyl)‐2,3‐epoxypropionate.
Remote biomedical spectroscopic imaging of human artery wall (1988)

We discuss a general technique, laser spectroscopic imaging (LSI), remote acquisition of spectroscopic images of biological tissues and tissue conditions. The technique employs laser-induced spectroscopic signals, collected and transmitted via an array of optical fibers, to produce discrete pixels of information from which a map or image of a desired tissue characteristic is constructed. We describe a prototype LSI catheter that produces spectral images of the interior of human arteries for diagnosis of atherosclerosis. The diagnostic is based on the fact that normal artery wall and atherosclerotic plaque exhibit distinct fluorescence spectra in the 500-650 nm range when excited by 476-nm laser light; the fluorescence from blood is minimal. The catheter is composed of 19 optical fibers enclosed in a transparent, protective shield. Argon ion laser radiation is used for excitation, and an optical multichannel spectral analyzer is used for detection. Sequential sampling is used to minimize crosstalk among fibers and reduce blurring of the image. Computer-processed 19-pixel spectroscopic images are produced of fresh cadaver artery in vitro. Regions of normal tissue, plaque, and blood are identified, and the diagnoses are confirmed histologically and by direct spatial correlation. The results demonstrate the concept of using this laser catheter system for real-time imaging.
Rho-Kinase vermittelt über Expression von TNF-α und CXC Chemokine die Leukozyten-Rekrutierung und die hepatozelluläre Apoptose bei septischem Leberschaden Rho kinase mediates leukocyte recruitment and hepatocellular apoptosis in septic liver injury via TNF-α and CXC chemokine expression (2006)

Due to the key role of the liver in metabolism and detoxification, manifestation of liver injury and liver failure represents a critical condition in the progression of sepsis, which is still associated with a high mortality. Rho kinase is known to control several cell functions including cell migration and adhesion as well as apoptosis, and its inhibition has been shown to be protective in hepatic and cardiac reperfusion injury in vivo. Herein, we investigated the potential role of Rho kinase and the protective effects of Rho kinase inhibition in endotoxin-induced liver injury in a mouse model. Male C57/BL6 mice were pretreated intraperitoneally with fasudil, a Rho kinase inhibitor, 15 min prior to lipopolysaccharide/D-galactosamine challenge. Six hours after pre-treatment, liver damage was quantified by intravital fluorescence microscopy of the left liver lobe and assessment of sinusoidal perfusion failure, sinusoidal and venular leukocyte recruitment, and hepatocellular apoptosis. Pre-treatment with fasudil showed a significant reduction of microcirculatory perfusion failure and hepatocellular apoptosis. Intrahepatic leukocyte rolling and adhesion were not significantly reduced, whereas histological analysis of leukocyte extravasation revealed a significant reduction in fasudil-pretreated animals. Thus, our study shows that Rho kinase plays a central role in septic liver injury, inducing microcirculatory derangements, leukocyte infiltration and hepatocellular apoptosis. Accordingly, Rho kinase inhibition might be a useful target in the therapy of septic liver injury.
One-step Preparation of BaTiO3 Nanoparticles by Liquid Source Chemical Vapor Deposition (2004)

Barium titanate (BaTiO3) nanoparticles were prepared by means of a liquid source chemical vapor deposition method under atmospheric pressure. The effects of precursor composition, concentration, operating temperature, and residence time in the hot zone on the surface morphology, composition, and crystallinity of the resulting particles were investigated. By increasing the Ba/Ti ratio in the precursor, the amount of TiO2 particles tended to decrease, while the amount of barium carbonate (BaCO3) particles increased. By decreasing the precursor concentration or the residence time in the hot zone, both particle size and degree of aggregation of the particles produced decreased, but the amount of barium carbonate increased. At a Ba/Ti ratio of 2.3, spherical and highly crystalline cubic BaTiO3 particles 27 nm in size with a narrow size distribution (σg = 1.33) were produced at 900°C.
Session 24 Integrating sensors and electronics: Where to draw the line? (1987)

Start of the above-titled section of the conference proceedings.
Additions and Corrections - Deriving Intermolecular Potential Functions for the Water Dimer from Ab Initio Calculations (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdditions and Corrections - Deriving Intermolecular Potential Functions for the Water Dimer from Ab Initio CalculationsWilliam JorgensenCite this: J. Am. Chem. Soc. 1980, 102, 25, 7619Publication Date (Print):December 1, 1980Publication History Published online20 February 2004Published inissue 1 December 1980https://pubs.acs.org/doi/10.1021/ja00545a608https://doi.org/10.1021/ja00545a608research-articleACS PublicationsRequest reuse permissionsArticle Views39Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A 0.008-mm<sup>2</sup> area-optimized thermal-diffusivity-based temperature sensor in 160-nm CMOS for SoC thermal monitoring (2014)

An array of temperature sensors based on the temperature-dependent thermal diffusivity of bulk silicon has been realized in a standard 160-nm CMOS process. The sensors achieve an inaccuracy of ±2.4 °C (3)) from −40 to 125 °C with no trimming and ±0.65 °C (3σ) with a one temperature trim. Each sensor occupies 0.008 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , and achieves a resolution of 0.21 °C (rms) at 1 kSa/s. This combination of accuracy, speed, and small size makes such sensors well suited for thermal monitoring in microprocessors and other systems-on-chip.
Carbon nanotube microfabricated window with extreme ultraviolet transmission and differential pumping (2022)

Hollow cathode plasmas are common extreme ultraviolet (EUV) lamps used for material characterization. However, the relatively high pressure of the plasma can affect downstream instruments, as well as absorb the EUV. EUV windows are difficult to fabricate due to EUV’s strong interaction with all materials. We present a carbon nanotube (CNT) microfabricated window composed of multiple high aspect-ratio columns in parallel. The open areas allow wide bandpass transmission, while the walls restrict gas flow. We model the CNT window transmission as a weight function on the light from of a Mcpherson 629-like hollow cathode helium plasma in visible wavelengths. We model the CNT window differential pumping as a series of columns between two chambers of different pressures.
Emergence of a New Swine H3N2 and Pandemic (H1N1) 2009 Influenza A Virus Reassortant in Two Canadian Animal Populations, Mink and Swine (2011)

A swine H3N2 (swH3N2) and pandemic (H1N1) 2009 (pH1N1) influenza A virus reassortant (swH3N2/pH1N1) was detected in Canadian swine at the end of 2010. Simultaneously, a similar virus was also detected in Canadian mink based on partial viral genome sequencing. The origin of the new swH3N2/pH1N1 viral genes was related to the North American swH3N2 triple-reassortant cluster IV (for hemagglutinin [HA] and neuraminidase [NA] genes) and to pH1N1 for all the other genes (M, NP, NS, PB1, PB2, and PA). Data indicate that the swH3N2/pH1N1 virus can be found in several pigs that are housed at different locations.
Experimental study of failure mechanisms in particle filled acrylic composites (2003)

Particle filled solid surface composites are used to fabricate kitchen countertops and sinks which may be subjected to severe temperature variations, giving rise to high thermal stresses. These stresses may lead to failure by cracking in regions subjected to large temperature variation. An aim of this paper is to investigate mechanisms of failure in solid surface materials using in situ observations during tensile, compressive and fatigue loading and to define test configurations that give meaningful measurements of material properties. Experiments show that the failure in tension occurs in several stages. In flexural loading the failure process is more complex. Consequently, flexural testing should not be used as a substitute for the measurement of ultimate tensile strength in a particle filled solid surface composite. The application of conventional damage mechanics to describe the failure of test specimens is also discussed.
Measurement of relative branching fractions of B decays to ψ(2S) and J/ψ mesons (2012)

The relative rates of <i>B</i>-meson decays into <i>J</i>/<i>ψ</i> and <i>ψ</i>(2<i>S</i>) mesons are measured for the three decay modes in <i>pp</i> collisions recorded with the LHCb detector. The ratios of branching fractions ([Formula: see text]) are measured to be [Formula: see text] where the third uncertainty is from the ratio of the <i>ψ</i>(2<i>S</i>) and <i>J</i>/<i>ψ</i> branching fractions to <i>μ</i><sup>+</sup><i>μ</i><sup>-</sup>.
Feasibility Study of Time-of-Flight Compton Scatter Imaging Using Picosecond Length X-Ray Pulses (2014)

By measuring the time of flight of scattered X-ray photons, the point of interaction, assuming a single scatter, can be determined, providing 3-D information about an object under inspection. This paper describes experimental ToF Compton scatter measurements conducted at the versatile electron linear accelerator (VELA), a picosecond pulsewidth electron source situated in Daresbury, U.K. The ToF of scattered X-ray photons was measured using a CeBr3 detector, and a full width at half maximum (FWHM) of between 29 and 36 cm was achieved with a 5-cm-thick plastic test object. By implementing a low-energy cutoff, the FWHM was reduced to between 12 and 26 cm. Two test objects placed in series with a 50-cm space between were separable in the data after applying the low energy cutoff.
Characterization of the Selective Indoleamine 2,3-Dioxygenase-1 (IDO1) Catalytic Inhibitor EOS200271/PF-06840003 Supports IDO1 as a Critical Resistance Mechanism to PD-(L)1 Blockade Therapy (2018)

Tumors use indoleamine 2,3-dioxygenase-1 (IDO1) as a major mechanism to induce an immunosuppressive microenvironment. IDO1 expression is upregulated in many cancers and considered to be a resistance mechanism to immune checkpoint therapies. IDO1 is induced in response to inflammatory stimuli such as IFNγ and promotes immune tolerance by depleting tryptophan and producing tryptophan catabolites, including kynurenine, in the tumor microenvironment. This leads to effector T-cell anergy and enhanced T<sub>reg</sub> function through upregulation of FoxP3. As a nexus for the induction of key immunosuppressive mechanisms, IDO1 represents an important immunotherapeutic target in oncology. Here, we report the identification and characterization of the novel selective, orally bioavailable IDO1 inhibitor EOS200271/PF-06840003. It reversed IDO1-induced T-cell anergy <i>in vitro</i> In mice carrying syngeneic tumor grafts, PF-06840003 reduced intratumoral kynurenine levels by over 80% and inhibited tumor growth both in monotherapy and, with an increased efficacy, in combination with antibodies blocking the immune checkpoint ligand PD-L1. We demonstrate that anti-PD-L1 therapy results in increased IDO1 metabolic activity thereby providing additional mechanistic rationale for combining PD-(L)1 blockade with IDO1 inhibition in cancer immunotherapies. Supported by these preclinical data and favorable predicted human pharmacokinetic properties of PF-06840003, a phase I open-label, multicenter clinical study (NCT02764151) has been initiated.
Data from Adult Low-Hypodiploid Acute Lymphoblastic Leukemia Emerges from Preleukemic <i>TP53</i>-Mutant Clonal Hematopoiesis (2023)

&lt;div&gt;Abstract&lt;p&gt;Low hypodiploidy defines a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL) with a dismal outcome. To investigate the genomic basis of low-hypodiploid ALL (LH-ALL) in adults, we analyzed copy-number aberrations, loss of heterozygosity, mutations, and cytogenetics data in a prospective cohort of Philadelphia (Ph)-negative B-ALL patients (&lt;i&gt;n&lt;/i&gt; = 591, ages 18–84 years), allowing us to identify 80 LH-ALL cases (14%). Genomic analysis was critical for evidencing low hypodiploidy in many cases missed by cytogenetics. The proportion of LH-ALL within Ph-negative B-ALL dramatically increased with age, from 3% in the youngest patients (under 40 years old) to 32% in the oldest (over 55 years old). Somatic &lt;i&gt;TP53&lt;/i&gt; biallelic inactivation was the hallmark of adult LH-ALL, present in virtually all cases (98%). Strikingly, we detected &lt;i&gt;TP53&lt;/i&gt; mutations in posttreatment remission samples in 34% of patients. Single-cell proteogenomics of diagnosis and remission bone marrow samples evidenced a preleukemic, multilineage, &lt;i&gt;TP53&lt;/i&gt;-mutant clone, reminiscent of age-related clonal hematopoiesis.&lt;/p&gt;Significance:&lt;p&gt;We show that low-hypodiploid ALL is a frequent entity within B-ALL in older adults, relying on somatic &lt;i&gt;TP53&lt;/i&gt; biallelic alteration. Our study unveils a link between aging and low-hypodiploid ALL, with &lt;i&gt;TP53-&lt;/i&gt;mutant clonal hematopoiesis representing a preleukemic reservoir that can give rise to aneuploidy and B-ALL.&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/bloodcancerdiscov/article/doi/10.1158/2643-3230.BCD-23-0006" target="_blank"&gt;See related commentary by Saiki and Ogawa, p. 102.&lt;/a&gt;&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/bloodcancerdiscov/article/doi/10.1158/2643-3230.BCD-4-2-ITI" target="_blank"&gt;This article is highlighted in the In This Issue feature, p. 101&lt;/a&gt;&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Development of Laser-Ion Beam Photodissociation Methods (2004)

OAK-B135 Our BES funded research is aimed at determining structure(s) of model gas-phase ions and understanding how structure influences unimolecular reactivity. The model gas-phase ions include positional isomers of di- and tri-amino acids synthesized in my laboratory, i.e., RGG, GRG, and GGR, to peptides derived from proteolytic digestion of biologically relevant proteins. We are especially interested in understanding the role of intramolecular interactions in the stabilizing ion structure and how changing the charge-site affects structure. The location of charge of gas-phase ions can be manipulated by changing the position of the charge carrying amino acid (basic vs. acidic side chains) and by derivatization of the N- and/or C-terminus. For example, the proton of [M + H]+ ions is mobile and migrates over the entire molecule, whereas Li+, Na+, and to some extent K+ prefers to bind to the C-terminal or side-chain carboxylic acid groups, and Cu+ binds exclusively to the N-terminus and/or basic side-chains such as H, K, and R. The studies are carried out using tandem TOF mass spectrometry, viz. 193 nm (6.43 eV) photodissociation, low (Elab = 10-100 eV) and high kinetic energy (Elab = 1-10 keV) collision-induced dissociation (CID) and surface-induced dissociation (SID)(Elab = 20-70 eV). These techniques are used to probe the structure of model gas-phase ions, i.e., to determine the amino acid sequence of the peptide ions or metal ion (alkali metal and/or transition metal ions) binding site(s) or the site(s) of other charge-carrying functional groups, i.e., oxidized side-chains as well as phosphate or sulfate groups. We are especially interested in understanding how metal ion binding alters the secondary/tertiary (2o/3o) structure of the peptide, i.e., intra-molecular interactions. We have also combine these studies with solution-phase studies and ion mobility spectrometry (IMS), which can be used to study 2o/3o structure of low-internal energy (collisionally stabilized) ions. It is difficult to probe 2o/3o structure of gas-phase ions using fragmentation chemistry, because the energy barriers to inter-conversion of different structural forms lie below the fragmentation threshold, studies of low internal energy ions are more suited for these studies. A major challenge for gas-phase ion research is the design of experimental structural probes that can be used in parallel with computational chemistry, molecular modeling and/or classical structural diagnostic tools to aid interpretation of the experimental data. Our experimental design and selection of research problems is guided by this philosophy. The following section of the progress report focus on three main issues: (i) technique and instrument development, and (ii) studies of ion structure and ion chemistry.