gebhart/patrepeval huggingface dataset:
Diastereoselective Reaction of a Grignard Reagent with Chiral Imides:  A Practical Preparation of a Key Intermediate in the Synthesis of Ifetroban Sodium (1997)

A novel and highly efficient synthesis of [1S-(1α,2α,3α,4α)]-2-[[2-(3-methoxy-3-oxopropyl)phenyl]methyl]-7-oxabicyclo[2.2.1]heptane-3-carboxylic acid (A), a key intermediate in the synthesis of ifetroban sodium, BMS-180291, is described. Reaction of chiral imides such as [2(S),3aα,4β,7β,7aα]-hexahydro-2-(1-phenylethyl)-4,7-epoxy-1H-isoindole-1,3(2H)-dione (B) with the Grignard reagent derived from 2-(2-bromophenyl)-1,3-dioxolane and subsequent in situ transformations give [2S-(2α,3aα,4β,7β,7aα)]-2-(octahydro-3-oxo-4,7-epoxyisobenzofuran-1-yl)benzaldehyde, converted in two steps to A. Efficient syntheses of B from furan and maleic anhydride are described.
Continuous Casting of Magnesium Alloy Billet Using Electromagnetic Techniques (2010)

Currently, magnesium billets produced by ingot casting or direct chill casting process, result in low-quality surfaces and peer productivity. Continuous casting technology for high-quality surface billets with fine-grained and homogeneous microstructure can be a solution for the cost barrier breakthrough. The latent heat of fusion per weight (J/g) of magnesium is similar to that of other metals, however, considering the heat emitted to the mould surface during continuous casting in meniscus region and converting it to the latent heat of fusion per volume, magnesium will be rapidly solidified in the mould during continuous casting, which induces subsequent surface defect formation. In this study, electromagnetic casting and stirring (EMC and EMS) techniques are proposed to control solidification process conveniently by compensating the low latent heat of solidification by volume and to fabricate magnesium billets with a high quality surface.
IDO Activates Regulatory T Cells and Blocks Their Conversion into Th17-Like T Cells (2009)

TLR ligands are effective vaccine adjuvants because they stimulate robust proinflammatory and immune effector responses and they abrogate suppression mediated by regulatory T cells (Tregs). Paradoxically, systemic administration of high doses of CpGs that bind to TLR9 ligands stimulated Tregs in mouse spleen to acquire potent suppressor activity dependent on interactions between programmed death-1 and its ligands. This response to CpG treatment manifested 8-12 h and was mediated by a rare population of plasmacytoid dendritic cells (CD19(+) pDC) induced to express the immunosuppressive enzyme IDO after TLR9 ligation. When IDO was blocked, CpG treatment did not activate Tregs, but instead stimulated pDCs to uniformly express the proinflammatory cytokine IL-6, which in turn reprogrammed Foxp3-lineage Tregs to express IL-17. Thus, CpG-induced IDO activity in pDCs acted as a pivotal molecular switch that induced Tregs to acquire a stable suppressor phenotype, while simultaneously blocking CpG-induced IL-6 expression required to reprogram Tregs to become Th17-like effector T cells. These findings support the hypothesis that IDO dominantly controls the functional status of Tregs in response to inflammatory stimuli in physiological settings.
Self-assembled electrical circuits and their electronic properties (2005)

A straightforward method for the self assembly of single walled carbon nanotubes (SWNTs) between gold electrodes was developed. The technique utilizes the hybridization between short complementary DNA sequences located on metal contacts and SWNTs. new technique enables simple production of hundreds of devices with high yields. The electrical characteristics are shown to depend strongly on the existence of the chemical binding groups at the contacts as well as along the tubes. This technique was used to drive the self assembly of SWNT-based field effect transistors (CNTFETs). In principle, the devices made by this method behave like those made using direct metal-carbon nanotube contacts. The inverse subthreshold slope of the CNTFETs depends on the source-drain voltage applied to the device, confirming that the conductance of CNTFETs is determined by the Schottky barriers at the interfaces between the CNTs and the gold electrodes.
Immunohistochemical marker panels for distinguishing between epithelioid mesothelioma and lung adenocarcinoma (2007)

The distinction between epithelioid mesothelioma and lung adenocarcinoma remains an important diagnostic challenge for surgical pathologists. The aim of the present study was to select a limited and appropriate panel of antibodies that can differentiate between epithelioid mesothelioma and lung adenocarcinoma. Specimens of 90 epithelioid mesotheliomas and 51 lung adenocarcinomas obtained from Japanese cases were examined using calretinin, WT1, AE1/AE3, CAM5.2, cytokeratin (CK) 5/6, vimentin, epithelial membrane antigen (EMA), thrombomodulin, CEA, CA19-9, and CA125. Ninety-six percent of epithelioid mesotheliomas were positive for calretinin; 99% for WT1; 100% for AE1/AE; 97% for CAM5.2; 70% for CK 5/6; 91% for vimentin; 96% for EMA; 71% for thrombomodulin; 77% for mesothelin; 7% for CEA; 17% for CA19-9; and 85% for CA125. In contrast, 33% of lung adenocarcinomas were positive for calretinin; 16% for WT1; 100% for AE1/AE3, CAM5.2, and EMA; 41% for CK 5/6; 47% for vimentin; 20% for thrombomodulin; 69% for mesothelin; 98% for CEA; 73% for CA19-9; and 80% for CA125. For distinguishing between epithelioid mesothelioma and lung adenocarcinoma, the combination of CEA, calretinin and each WT1 or thrombomodulin was suggested to be the best panel of immunohistochemical markers.
Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice (2007)

We previously demonstrated that artificial lymph nodes (aLNs) could be generated in mice by the implantation of stromal cell-embedded biocompatible scaffolds into their renal subcapsular spaces. T and B cell domains that form in aLNs have immune response functions similar to those of follicles of normal lymphoid tissue. In the present study, we show that the aLNs were transplantable to normal as well as SCID mice, where they efficiently induced secondary immune responses. Antigen-specific secondary responses were strongly induced in aLNs even 4 weeks after their transplantation. The antigen-specific antibody responses in lymphocyte-deficient SCID mice receiving transplanted aLNs were substantial. The cells from the aLNs migrated to the SCID mouse spleen and BM, where they expanded to generate large numbers of antigen-specific antibody-forming cells. Secondary responses were maintained over time after immunization (i.e., antigen challenge), indicating that aLNs can support the development of memory B cells and long-lived plasma cells. Memory CD4(+) T cells were enriched in the aLNs and spleens of aLN-transplanted SCID mice. Our results indicate that aLNs support strong antigen-specific secondary antibody responses in immunodeficient mice and suggest the possibility of future clinical applications.
Formation of Complement Membrane Attack Complex in Mammalian Cerebral Cortex Evokes Seizures and Neurodegeneration (2003)

The complement system consists of >30 proteins that interact in a carefully regulated manner to destroy invading bacteria and prevent the deposition of immune complexes in normal tissue. This complex system can be activated by diverse mechanisms proceeding through distinct pathways, yet all converge on a final common pathway in which five proteins assemble into a multimolecular complex, the membrane attack complex (MAC). The MAC inserts into cell membranes to form a functional pore, resulting in ion flux and ultimately osmotic lysis. Immunohistochemical evidence of the MAC decorating neurons in cortical gray matter has been identified in multiple CNS diseases, yet the deleterious consequences, if any, of MAC deposition in the cortex of mammalian brain in vivo are unknown. Here we demonstrate that the sequential infusion of individual proteins of the membrane attack pathway (C5b6, C7, C8, and C9) into the hippocampus of awake, freely moving rats induced both behavioral and electrographic seizures as well as cytotoxicity. The onset of seizures occurred during or shortly after the infusion of C8/C9. Neither seizures nor cytotoxicity resulted from the simultaneous infusion of all five proteins premixed in vitro. The requirement for the sequential infusion of all five proteins together with the temporal relationship of seizure onset to infusions of C8/C9 implies that the MAC was formed in vivo and triggered both seizures and cytotoxicity. Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain.
Targeting‐Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy (2014)

Photodynamic therapy (PDT) and photothermal therapy (PTT) possess advantages over the conventional therapies with additional treatment selectivity achieved with local laser irradiation. Comparing to PTT that ablates target tissue via thermal necrosis, PDT induces target cell death via singlet oxygen without damaging the underling connective tissue, thus preserving its biological function. Activatable photosensitizers provide an additional level of treatment selectivity via the disease-associated activation mechanism. In this study, folate-conjugated porphysomes are introduced as targeting-triggered activatable nano-sized beacons for PDT. Porphysomes are reported previously as the most stable and efficient delivery system of porphyrin, but their nanostructure converts the singlet oxygen generation mechanism to thermal ablation mechanism. By folate-receptor-mediated endocytosis, folate-porphysomes are internalized into cells rapidly and resulted in efficient disruption of nanostructures, thus switching back on the photodynamic activity of the densely packed porphyrins for effective PDT. In both in vitro and in vivo studies, folate-porphysomes can achieve folate receptor-selective PDT efficacy, which proves the robustness of targeting-triggered PDT activation of porphysome nanostructure for highly selective tumor ablation. The formulation of porphysomes can be modified with other targeting ligands as activatable photosensitizers for personalized treatment in future.
Current Progress in the Production of Recombinant Human Fibrinogen in the Milk of Transgenic Animals (1997)

The mammary gland of transgenic animals has several advantages for production of heterologous proteins including a high cell density that results in high concentrations of secreted protein. While the mammary gland appears to be able to secrete fully assembled recombinant human fibrinogen (rhfib) at 0.1 to 5 g/l levels, some unassembled rhfib chains are also secreted. Presently, the relationship between unassembled rhfib and the coordinated translation of each nascent rhfib polypeptide in the mammary epithelia is unknown. The secretion of fully and partially assembled rhfib is widely variable among mammalian cell lines and where previously no cell line has been shown to secrete beta chain alone. We have observed that mammary epithelia can secrete B beta chain into milk as well as immature forms of other recombinant proteins, suggesting it likely uses a different secretory pathway than does the liver. This difference in secretory behavior is possibly due to the natural design of milk, where the precise regulation of post translational modifications and intracellular pools of nascent polypeptides needed to achieve fibrinogen assembly may be less important to fulfill the nutritional function of most milk proteins.
Elucidating the role of surface passivating ligand structural parameters in hole wave function delocalization in semiconductor cluster molecules (2017)

This article describes the mechanisms underlying electronic interactions between surface passivating ligands and (CdSe)<sub>34</sub> semiconductor cluster molecules (SCMs) that facilitate band-gap engineering through the delocalization of hole wave functions without altering their inorganic core. We show here both experimentally and through density functional theory calculations that the expansion of the hole wave function beyond the SCM boundary into the ligand monolayer depends not only on the pre-binding energetic alignment of interfacial orbitals between the SCM and surface passivating ligands but is also strongly influenced by definable ligand structural parameters such as the extent of their π-conjugation [π-delocalization energy; pyrene (Py), anthracene (Anth), naphthalene (Naph), and phenyl (Ph)], binding mode [dithiocarbamate (DTC, -NH-CS<sub>2</sub><sup>-</sup>), carboxylate (-COO<sup>-</sup>), and amine (-NH<sub>2</sub>)], and binding head group [-SH, -SeH, and -TeH]. We observe an unprecedentedly large ∼650 meV red-shift in the lowest energy optical absorption band of (CdSe)<sub>34</sub> SCMs upon passivating their surface with Py-DTC ligands and the trend is found to be Ph- < Naph- < Anth- < Py-DTC. This shift is reversible upon removal of Py-DTC by triethylphosphine gold(i) chloride treatment at room temperature. Furthermore, we performed temperature-dependent (80-300 K) photoluminescence lifetime measurements, which show longer lifetime at lower temperature, suggesting a strong influence of hole wave function delocalization rather than carrier trapping and/or phonon-mediated relaxation. Taken together, knowledge of how ligands electronically interact with the SCM surface is crucial to semiconductor nanomaterial research in general because it allows the tuning of electronic properties of nanomaterials for better charge separation and enhanced charge transfer, which in turn will increase optoelectronic device and photocatalytic efficiencies.
Overexpression of a designed 2.2 kb gene of eukaryotic phenylalanine ammonia‐lyase in Escherichia coli (1999)

Phenylalanine ammonia-lyase (EC 4.3.1.5) is a key enzyme in the secondary metabolism of higher plants catalyzing the non-oxidative conversion of L-phenylalanine into transcinnamate. The nucleotide sequence of its 2.2 kb gene was designed for expression in Escherichia coli and synthesized in a single reaction from 108 oligonucleotides using assembly PCR. After amplification, the gene was cloned into the expression vector pT7-7 and coexpressed with the chaperone HSP-60 system. The expression system yielded 70 mg of fully active enzyme per liter culture.
Combined action of static and alternating magnetic fields on ion motion in a macromolecule: Theoretical aspects (1998)

This is an attempt to solve the energetic problem of the primary detection of weak parallel static (DC) and alternating (AC) extremely low frequency (ELF) magnetic fields. We studied the equations of motion for an ion situated inside a macromolecule under the influence of these fields. The main concern is with the magnetic field influence on thermal motion of the ion in the macromolecule. The resonance effects are revealed at discrete frequencies of the ion thermal oscillations determined by the DC field magnitude and the AC field frequency. These phenomena result from the Larmor precession of the ion thermal motion. When the DC field or, to a greater extent, the combined DC and AC fields with the specific frequencies are turned on or cut off, changes occur in the energy of the ion thermal motion. If, inside the macromolecule, the ion is sufficiently protected against immediate impacts of particles of the medium surrounding the macromolecule, these changes may be enough to trigger alteration in the quantum state of the macromolecule.
Cellular Antioxidant Effects of Atorvastatin In Vitro and In Vivo (2002)

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert direct effects on vascular cells and beneficially influence endothelial dysfunction. Because reactive oxygen species (ROS) may lead to vascular damage and dysfunction, we investigated the effect of atorvastatin on ROS production and the underlying mechanisms in vitro and in vivo. Cultured rat aortic vascular smooth muscle cells were incubated with 10 micromol/L atorvastatin. Angiotensin II-induced and epidermal growth factor-induced ROS production were significantly reduced by atorvastatin (dichlorofluorescein fluorescence laser microscopy). Atorvastatin downregulated mRNA expression of the NAD(P)H oxidase subunit nox1, whereas p22phox mRNA expression was not significantly altered (reverse transcription-polymerase chain reaction, Northern analysis). Membrane translocation of rac1 GTPase, which is required for the activation of NAD(P)H oxidase, was inhibited by atorvastatin (Western blot). mRNA expression of superoxide dismutase isoforms and glutathione peroxidase was not modified by atorvastatin, whereas catalase expression was upregulated at mRNA and protein levels, resulting in an increased enzymatic activity. Effects of atorvastatin on ROS production and nox1, rac1, and catalase expression were inhibited by L-mevalonate but not by 25-hydroxycholesterol. In addition, spontaneously hypertensive rats were treated with atorvastatin for 30 days. ROS production in aortic segments was significantly reduced in statin-treated rats (lucigenin chemiluminescence). Treatment with atorvastatin reduced vascular mRNA expression of p22phox and nox1 and increased aortic catalase expression. mRNA expression of superoxide dismutases, glutathione peroxidase, and NAD(P)H oxidase subunits gp91phox, p40phox, p47phox, and p67phox remained unchanged. Translocation of rac1 from the cytosol to the cell membrane was also reduced in vivo. Thus, atorvastatin exerts cellular antioxidant effects in cultured rat vascular smooth muscle cells and in the vasculature of spontaneously hypertensive rats mediated by decreased expression of essential NAD(P)H oxidase subunits and by upregulation of catalase expression. These effects of atorvastatin may contribute to the vasoprotective effects of statins.
Treprostinil sodium Pharmacia. (2002)

United Therapeutics Corp (UTC) is developing treprostinil sodium (Remodulin, UT-15), a stable structural analog of prostacyclin, for the potential treatment of primary pulmonary (arterial) hypertension (PAH), peripheral vascular disease (PVD) and other cardiovascular conditions [327593], including critical limb ischemia (CLI) [412483]. In August 2000, UTC submitted the initial, non-clinical sections of an NDA for the treatment of pulmonary hypertension [378906]. Treprostinil, which had previously been designated as an Orphan Drug, was also awarded Priority Review status by the US FDA in October 2000 [385864], [386271]. In December 2000, UTC agreed with the FDA that the NDA for treprostinil did not need to be presented to the Cardiovascular and Renal Drugs Advisory Committee, which was expected to allow UTC and the FDA to work towards the 6-month Priority Review timeline [393888]. On August 9, 2001, the advisory committee recommended approval of treprostinil and UTC refiled the NDA on the same day [418682]. In February 2002, the FDA issued an approvable letter for treprostinil injection for the treatment of PAH. The FDA proposed drug labeling for PAH consistent with the treatment of both primary and secondary pulmonary hypertension in patients with New York Heart Association (NYHA) Class II-IV symptoms. The approvable letter also stated that the FDA intended to approve treprostinil with a requirement that UTC subsequently conduct a post-marketing controlled clinical trial to verify and further describe the drug's clinical benefit [439278]. In February 2001, UTC submitted a marketing authorization application (MAA) in France for approval of treprostinil for the treatment of PAH. Upon approval of the MAA, UTC planned to file for Mutual Recognition in other European countries and was also preparing similar submissions to non-European countries [391986], [397958]. By early 2001, phase II trials of treprostinil for the treatment of CLI were underway [412483]. In March 2001, the company was planning a phase III pivotal study in late-stage PVD by the end of 2001 [424180]. In April 2000, UTC was issued US-06054486 for the method of treating PVD with treprostinil [364130]. In February 2000, UTC entered into an agreement with Paladin Labs for the exclusive Canadian distribution of treprostinil for the remainder of clinical trials and after regulatory approvals [357302]. In November 2000, UTC and Antigen Pharmaceuticals entered into a strategic alliance for the distribution of treprostinil in the UK and Ireland [390157]. In November 2000, Deutsche Banc Alex Brown predicted a sales potential of US $250 million to US $350 million [418736]. In August 2001, Merril Lynch predicted sales of US $10 million to $20 million in 2002 [420652].
Reverse vaccinology: a critical analysis (2005)

Abstract Reverse vaccinology is a relatively new approach aimed at facilitating and accelerating the discovery of vaccine candidates. It basically consists of the exploitation of genome sequences to predict, among all available genes, those ones encoding proteins likely to represent the targets of protective immune responses (surface‐associated proteins, virulence factors, toxins, etc.). Once predictions are made, selected proteins are recombinantly expressed, purified, and finally tested in correlate‐of‐protection assays to ultimately identify the protective antigens. Since its first published successful application (Pizza et al. , ), reverse vaccinology has been applied to several bacterial pathogens with promising results. The scope of this review is to describe a few examples of this technology, highlighting the main achievements. In addition, the review also examines the critical aspects of the technology and attempts to draw a series of guidelines for future improvements.
Assessment of the duration of action of terfenadine on histamine induced weals (1988)

In this study we aimed to quantify the reduction in area, perimeter and thickness of histamine induced weals 12, 18 and 24 h after a single oral dose of 120 mg terfenadine. Ten healthy volunteers were given 120 mg of terfenadine or placebo in a double-blind randomized two-period cross-over study. Twenty micrograms of histamine were then injected intradermally at 12, 18, and 24 h. The thickness of the resulting weal was measured by an A-scan pulsed ultrasound device. The area and perimeter of the resulting weal and flare were measured by tracing onto acetate sheets and using a digitizing tablet linked to a microcomputer. Just before each dose of histamine was injected, blood was taken to measure the level of the major metabolite of terfenadine. There was a significant difference between terfenadine 120 mg and placebo in the area and perimeter of the weal and the area and perimeter of the weal and flare at 12, 18 and 24 h, but no significant difference in weal thickness. Thus, terfenadine suppresses the wealing response caused by intradermally injected histamine over a 24 h period. It may be possible, therefore, to use a once daily dose of terfenadine.