gebhart/patrepeval huggingface dataset:
Living Coupling Reaction in Living Cationic Polymerization. 3. Coupling Reaction of Living Polyisobutylene Using Bis(furanyl) Derivatives (2000)

Living coupling reactions of living polyisobutylene (PIB) with bis(furanyl) compounds, 2,2-difurylmethane (DFM), 2,5-bis(2-furylmethyl)furan (bFMF), 2,2-difurylpropane (DFP), and 2,5-bis(2-furyl-2-propyl)furan (bFPF) were investigated in the presence of TiCl4 as Lewis acid in hexanes/CH3Cl 60/40 and 40/60 (v/v) at −80 °C and with bFPF in conjunction with BCl3 in CH3Cl at −40 °C. The products obtained with DFM and bFMF were slightly colored most probably due to α-hydride abstraction and the development of conjugated structures. DFP and bFPF, lacking α-hydrogens, yielded colorless products. In hexanes/CH3Cl 60/40 (v/v), coupling was very slow and incomplete after 2 h with DFM and DFP, which was ascribed to deactivation of the second furanyl ring after monoaddition. Coupling was faster with bFMF; however, the coupling efficiency was only 85% after 2 h due to some side reactions that consumed bFMF. Coupling was rapid and quantitative with bFPF in the presence of TiCl4 in hexanes/CH3Cl 60/40 (v/v) at −80 °C. Increasing the solvent polarity to hexanes/CH3Cl 40/60 (v/v) further increased the rate by 2-fold. Efficient, albeit slow, coupling was also achieved with bFPF in CH3Cl at −40 °C in the presence of BCl3. The mechanism of the coupling reaction was investigated in the presence of TiCl4 in hexanes/CH3Cl 60/40 (v/v) at −80 °C by quenching the reaction mixture with tributyltin hydride after complete coupling had been achieved. Identification of the product structure by 1H NMR spectroscopy verified the formation of stable dications upon coupling and confirmed that this reaction is a living coupling reaction.
Effect of Vagotomy on the Breathing Pattern and Exercise Ability in Emphysematous Patients (1982)

1. The potential value of right vagotomy for the relief of breathlessness has been explored in five patients with emphysema. Two patients had symptomatic improvement, two had minor symptomatic improvement, and one was unchanged. 2. Exercise ventilation was not noticeably depressed by unilateral right vagotomy in the two patients investigated fully, but the pattern of breathing was altered. After vagotomy, breathing was deeper, and the rise in the frequency of breathing with exercise was depressed. 3. After right vagotomy the response to rebreathing carbon dioxide also consisted of slower deeper breaths. 4. Right vagotomy sometimes appears to remove an influence preventing slow deep breathing and exacerbating dyspnoea. 5. Results of bilateral pulmonary denervation, attempted in one patient, were complicated by the need for left thoracotomy, which removed any possible beneficial effects.
High Bone Mass in Mice Expressing a Mutant LRP5 Gene (2003)

A unique mutation in LRP5 is associated with high bone mass in man. Transgenic mice expressing this LRP5 mutation have a similar phenotype with high bone mass and enhanced strength. These results underscore the importance of LRP5 in skeletal regulation and suggest targets for therapies for bone disease. A mutation (G171V) in the low-density lipoprotein receptor related protein 5 (LRP5) has been associated with high bone mass (HBM) in two independent human kindreds. To validate the role of the mutation, several lines of transgenic mice were created expressing either the human LRP5 G171V substitution or the wildtype LRP5 gene in bone. Volumetric bone mineral density (vBMD) analysis by pQCT showed dramatic increases in both total vBMD (30-55%) and trabecular vBMD (103-250%) of the distal femoral metaphysis and increased cortical size of the femoral diaphysis in mutant G171V transgenics at 5, 9, 17, 26, and 52 weeks of age (p < 0.01 for all). In addition, high-resolution microcomputed tomography (microCT) analysis of the distal femorae and lumbar vertebrae revealed an increase (110-232%) in trabecular bone volume fraction caused by both increased trabecular number (41-74%) and increased trabecular thickness (34-46%; p < 0.01 for all) in the mutant G171V mice. The increased bone mass was associated with significant increases in vertebral compressive strength (80-140%) and the increased cortical size with significant increases in femoral bending strength (50-130%). There were no differences in osteoclast number at 17 weeks of age. However, compared with littermate controls, the mutant G171V transgenic mice showed an increase in actively mineralizing bone surface, enhanced alkaline phosphatase staining in osteoblasts, and a significant reduction in the number of TUNEL-positive osteoblasts and osteocytes. These results suggest that the increased bone mineral density in mutant G171V mice was caused by increased numbers of active osteoblasts, which could in part be because of their increased functional lifespan. While slight bone anabolic activity was observed from overexpression of the wildtype LRP5 gene, it is clear that the G171V mutation, rather than overexpression of the receptor itself, is primarily responsible for the dramatic HBM bone effects. Together, these findings establish the importance of this novel and unexpected role of a lipoprotein receptor in regulating bone mass and afford a new model to explore LRP5 and its recent association with Wnt signaling in bone biology.
Suppression of Ongoing Disease in a Nonhuman Primate Model of Multiple Sclerosis by a Human-Anti-Human IL-12p40 Antibody (2005)

IL-12p40 is a shared subunit of two cytokines with overlapping activities in the induction of autoreactive Th1 cells and therefore a potential target of therapy in Th1-mediated diseases. We have examined whether ongoing disease in a nonhuman primate model of multiple sclerosis (MS) can be suppressed with a new human IgG1kappa Ab against human IL-12p40. Lesions developing in the brain white matter were visualized and characterized with standard magnetic resonance imaging techniques. To reflect the treatment of MS patients, treatment with the Ab was initiated after active brain white matter lesions were detected in T2-weighted images. In placebo-treated control monkeys we observed the expected progressive increase in the total T2 lesion volume and markedly increased T2 relaxation times, a magnetic resonance imaging marker of inflammation. In contrast, in monkeys treated with anti-IL-12p40 Ab, changes in the total T2 lesion volume and T2 relaxation times were significantly suppressed. Moreover, the time interval to serious neurological deficit was delayed from 31 +/- 10 to 64 +/- 20 days (odds ratio, 0.312). These results, in a disease model with high similarity to MS, are important for ongoing and planned trials of therapies that target IL-12 and/or IL-23.
Thymidine arrest and synchrony of cellular growth in vivo. (1980)

Thymidine (TdR) has been used to study the kinetics of in vitro cell proliferation and is currently being used clinically as a single agent at high doses. We have explored the in vivo cytokinetic effects of TdR on rapidly proliferating cell populations by continuous infusions in rats. The nucleoside was lethal at high doses when serum levels approached 10(-2) M.. At levels of 10(-3) M, TdR exposure for greater than 24 hours resulted in bone marrow hypocellularity and peripheral myelosuppression. Pathologic findings were also noted in the intestinal mucosa. Serum TdR levels of 10(-4) M were sufficient to induce arrest of cell growth in S phase by inhibition of DNA synthesis. Subsequent release after TdR exposure produced partial synchronization of the bone marrow and intestinal mucosa cell populations, as shown by microfluorometry and labeling studies to monitor DNA synthesis. A similar arrest of cell cycle traverse has been demonstrated in a tumor cell population by infusing rats bearing transplantable subcutaneous myeloblastomas. The inhibition of DNA synthesis, as determined by labeling studies, was comparable for bone marrow, intestinal mucosa, and myeloblastoma at serum TdR levels of 10(-3) M. This arrest of myeloblast cell growth was dependent on tumor burden and did not effect survival when maintained during 72-hour infusions. The continuous infusion of TdR provides an approach for studying cell kinetics in vivo, and findings similar to those described here have been observed in our clinical studies.
Novel thermooxidatively stable poly(ether‐imide‐benzoxazole) and poly(ester‐imide‐benzoxazole) (1994)

Abstract 4‐Hydroxy‐5‐nitrophthalimides were produced via nucleophilic aromatic substitution (NAS) of 4,5‐dichloro phthalimide substituents by potassium nitrite. The use of a N ‐phenyl‐phthalimide having a protected 4′‐hydroxyl group allows concurrent deprotection and nitro reduction to amine to give the 4‐hydroxy‐5‐amino‐ N ‐(4′‐hydroxyphenyl) phthalimide. This key intermediate is the precursor to a poly (ether‐imide‐benzoxazole), and is the condensable monomer for a poly (ester‐imide‐benzoxazole). Benzoxazole monomer formation via condensation with p ‐fluorobenzoyl chloride afforded 2‐(4′‐fluorophenyl)‐5,6,‐ N ‐[4′(‐hydroxyphenyl) imide]‐benzoxazole, which was polymerized under NAS conditions to produce a poly(ether‐imide‐benzoxazole) having an endothermic transition at 454°C with weight retention of 90% at 500°C in both air and nitrogen. Solution polycondensation of the 4‐hydroxy‐5‐amino‐ N ‐(4′‐hydroxyphenyl) phthalimide monomer with isophthaloyl chloride afforded a poly(ester‐amide‐imide) which was isolated and thermally cyclodehydrated in the solid state under vacuum to give a poly(ester‐imide‐benzoxazole) having 95% weight retention at 500°C in both air and nitrogen, with no detectable DSC transitions up to 500°C. © 1994 John Wiley &amp; Sons, Inc.
Phase II study of bendamustine in patients with relapsed or cisplatin-refractory germ cell cancer (2000)

Despite generally high cure rates in patients with metastatic germ cell cancer, patients with incomplete response to first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. We investigated the efficacy and toxicity of bendamustine, a bifunctional alkylating benzimidol derivative with only partial cross-resistance to other alkylating agents such as ifosfamide or cyclophosphamide. Nineteen patients with cisplatin-refractory germ cell tumors (GCT) or relapse after high-dose chemotherapy plus autologous stem cell support were treated with bendamustine at a dose of 120 mg/m2 on 2 consecutive days at 3 week intervals. Patients had received a median of 9 (range 4-20) platinum-containing treatment cycles prior to bendamustine and 13 patients (68%) had previously received carboplatin/etoposide-based high-dose chemotherapy. One patient achieved a partial remission of only 6 weeks duration. No other responses were seen. Toxicity was low with one patient developing WHO grade 3 thrombocytopenia as the only WHO grade 3/4 toxicity observed. Hematologic toxicity was similar in patients pretreated with and without high-dose chemotherapy plus autologous stem cell support. We conclude that bendamustine has little or no clinically relevant activity in patients with cisplatin-refractory GCT or relapsed disease after high-dose chemotherapy.
Evaluation of the Effectiveness of Wet Ice, Dry Ice, and Cryogen Packs in Reducing Skin Temperature (1987)

The purposes of this study were to evaluate and compare the ability of wet ice (WI), dry ice (DI), and cryogenic packs (CGPs) to reduce and maintain the reduction of skin temperature directly under the cooling agent and to determine whether the cooling effect on skin extended beyond the surface area in contact with the cooling agent. Ten female volunteers participated in the study, and each of the three cold modalities was applied randomly to the skin overlying the right triceps surae muscle. After 15 minutes of cold application, mean skin temperatures recorded under WI, DI, and CGP decreased 12 degrees, 9.9 degrees, and 7.3 degrees C, respectively. The only significant differences in cooling were between WI and DI and between WI and CGP. Fifteen minutes after removal of the cold modalities, no significant differences were found in mean skin temperature between WI, DI, and CGP. The residual mean decrease in skin temperature between the pretreatment rest interval (time 0) and 15 minutes after removal of the cold modality (time 30) was significant for WI only. No cooling was demonstrated 1 cm proximal or distal to any of the cooling agents after 15 minutes of cold application. These findings provide valuable information for the use of cryotherapy in the clinical setting.
Immune checkpoint protein VISTA regulate autoimmunity and anti-tumor immunity (P2069) (2013)

Abstract V-domain Ig Suppressor of T cell Activation (VISTA) is a newly discovered immune checkpoint ligand that suppresses T cell activation. Our study demonstrates the critical role of VISTA in controlling autoimmunity and anti-tumor immunity. Within the hematopoietic compartment, VISTA is highly expressed on myeloid antigen-presenting cells, naïve T cells and Foxp3+ Tregs. Aged VISTA ko mice developed inflammatory phenotypes. When bred onto a TCR transgenic background that is specific for myelin oligodendrocyte glycoprotein (MOG), VISTA ko mice developed severe autoimmune disease at 6-7 weeks of age. VISTA also regulates the suppressive function of Foxp3+CD4+ regulatory T cells (Tregs), as well as the induction of adaptive Tregs in the periphery. During tumor development, VISTA expression is upregulated within the tumor microenvironment. A VISTA-specific monoclonal antibody (mab)-mediated blockade enhanced tumor-specific T cell priming, as well as altered the suppressive character of the tumor microenvironment by reducing tumor-infiltration of myeloid-derived suppressor cells while enhancing the infiltration and effector function of tumor-specific effector T cells. Consequently, VISTA mab-mediated blockade as a single reagent significantly suppressed the growth of both transplantable and inducible melanoma tumors, and when combined with a cancer vaccine, effectively eradicated established tumors. VISTA thus represents a novel and promising target for cancer immunotherapy.
Elemental Fluorine in Organic Chemistry (1997—2006) (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Response of Retinal Connexin43 to Optic Nerve Injury (2011)

A biphasic upregulation of retinal Cx43 protein occurs in the superior retina with peaks at 3 and 28 days after injury, but at only 28 days in the inferior retina. There is an associated loss of RGCs and a retinal astrocytic inflammatory response.
Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors (1998)

The mechanism of superoxide generation by endothelial nitric oxide synthase (eNOS) was investigated by the electron spin resonance spin-trapping technique using 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide. In the absence of calcium/calmodulin, eNOS produces low amounts of superoxide. Upon activating eNOS electron transfer reactions by calcium/calmodulin binding, superoxide formation is increased. Heme-iron ligands, cyanide, imidazole, and the phenyl(diazene)-derived radical inhibit superoxide generation. No inhibition is observed after addition of L-arginine, NG-hydroxy-L-arginine, L-thiocitrulline, and L-NG-monomethyl arginine to activated eNOS. These results demonstrate that superoxide is generated from the oxygenase domain by dissociation of the ferrous-dioxygen complex and that occupation of the L-arginine binding site does not inhibit this process. However, the concomitant addition of L-arginine and tetrahydrobiopterin (BH4) abolishes superoxide generation by eNOS. Under these conditions, L-citrulline production is close to maximal. Our data indicate that BH4 fully couples L-arginine oxidation to NADPH consumption and prevents dissociation of the ferrous-dioxygen complex. Under these conditions, eNOS does not generate superoxide. The presence of flavins, at concentrations commonly employed in NOS assay systems, enhances superoxide generation from the reductase domain. Our data indicate that modulation of BH4 concentration may regulate the ratio of superoxide to nitric oxide generated by eNOS.
Do Mitochondriotropic Antioxidants Prevent Chlorinative Stress-Induced Mitochondrial and Cellular Injury? (2007)

Reactive chlorine species such as hypochlorous acid (HOCl) are cytotoxic oxidants generated by activated neutrophils at the sites of chronic inflammation. Since mitochondria are key mediators of apoptosis and necrosis, we hypothesized that mitochondriotropic antioxidants could limit HOCl-mediated intracellular oxidative injury to human fetal liver cells, preserve mitochondrial function, and prevent cell death. In this current study, we show that recently developed mitochondria-targeted antioxidants (MitoQ and SS31) significantly protected against HOCl-induced mitochondrial damage and cell death at concentrations >or=25 nM. Our study highlights the potential application of mitochondria-specific targeted antioxidants for the prevention of cellular dysfunction and cell death under conditions of chlorinative stress, as occurs during chronic inflammation.
Multiscalar processors (1995)

Multiscalar processors use a new, aggressive implementation paradigm for extracting large quantities of instruction level parallelism from ordinary high level language programs. A single program is divided into a collection of tasks by a combination of software and hardware. The tasks are distributed to a number of parallel processing units which reside within a processor complex. Each of these units fetches and executes instructions belonging to its assigned task. The appearance of a single logical register file is maintained with a copy in each parallel processing unit. Register results are dynamically routed among the many parallel processing units with the help of compiler-generated masks. Memory accesses may occur speculatively without knowledge of preceding loads or stores. Addresses are disambiguated dynamically, many in parallel, and processing waits only for true data dependences.This paper presents the philosophy of the multiscalar paradigm, the structure of multiscalar programs, and the hardware architecture of a multiscalar processor. The paper also discusses performance issues in the multiscalar model, and compares the multiscalar paradigm with other paradigms. Experimental results evaluating the performance of a sample of multiscalar organizations are also presented.
Single-Crystalline Star-Shaped Nanocrystals and Their Evolution:  Programming the Geometry of Nano-Building Blocks (2002)

We demonstrate a novel synthetic scheme that can be used to differentially guide the shape of PbS semiconductor nanocrystals. Our study first demonstrates the discovery of single-crystalline star-shaped nanocrystals as novel transient species. We then carefully probe their shape evolution toward other novel nanostructures (e.g., tadpole-, L-, T-, cross-shapes, highly faceted star shapes, truncated octahedrons and cubes, etc.) and systematically elucidate the key parameters that control these final structures. In principle, through programming these growth parameters, the desired architecture of building blocks of other kinds of nano materials can be constructed.
Autocrine BDNF Secretion Enhances the Survival and Serotonergic Differentiation of Raphe Neuronal Precursor Cells Grafted into the Adult Rat CNS (1996)

RN46A cells are a temperature-sensitive neuronal cell line derived from the E13 rat raphe nucleus. RN46A cells grafted into the adult rat hippocampus and cerebral cortex do not survive beyond 2 weeks. Brain-derived neurotrophic factor (BDNF) regulates the in vitro survival and serotonergic phenotype of RN46A cells, and we hypothesized that expression of BDNF in RN46A cells would potentiate their survival and serotonin (5HT) expression in vivo. The gene encoding rat BDNF was transfected into RN46A cells and the clonal 46A-B14 cell line isolated, 46A-B14 cells synthesize and secrete biologically active BDNF in vitro and synthesize 5HT following partial membrane depolarization. Two weeks following 46A-B14 cell transplantation into the adult rat cortex and hippocampus, there is a threefold increase in survival of 46A-B14 cells compared to RN46A cells transfected with the vector alone. The grafted 46A-B14 cells immunohistochemically stain for BDNF and 5HT, while RN46A cells transfected with vector only are negative for both BDNF and 5HT. In addition, 46A-B14 cells attain more morphologically complex phenotypes, indicating enhanced neuronal differentiation. Autocrine secretion of BDNF by RN46A cells thus potentiates survival and can be used to deliver both BDNF and 5HT in vivo.
Recent Results in the Search for New Molecules with Ambergris Odor (2014)

The synthesis of new odorant molecules is still a challenging task for the fragrance chemist, because now as ever it is difficult to predict the odor properties of small organic molecules. Therefore, certain tools, such as, e.g., lead-structure optimization of existing odorants, are helpful techniques. In this article, we describe the synthesis and the odor properties of a new molecule derived by the so-called 'seco' lead-structure optimization of the ambergris compound Ambroxide(®) . Based on these results, more representatives with similar structures have been synthesized and evaluated for their olfactory properties.
Oral processing of heterogeneous foods : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Food Science at Massey University, New Zealand (2011)

Food manufacturers could potentially benefit from foods designed to influence&#13;\nmastication and the breakdown of food into a bolus. Mastication and the properties of&#13;\nthe food bolus have been linked to the sensory and nutritional properties of foods. This&#13;\nresearch aimed to investigate the mastication and particle size distribution of the food&#13;\nbolus of heterogeneous food systems, where one food component is combined with&#13;\nanother, with a view to indentifying parameters that influence mastication and the food&#13;\nbolus. A range of matrices of contrasting physical properties, which were embedded&#13;\nwith peanut pieces of contrasting physical properties, were investigated.&#13;\nTrials involved serving these heterogeneous foods to subjects standardized by volume&#13;\n(concluded as the most suitable serving method following an investigation of natural&#13;\nbite size). Subjects were asked to chew and expectorate the bolus (where the number of&#13;\nchews and chewing time were recorded) before the matrix of the expectorated bolus was&#13;\nwashed away to isolate the peanut particles, and the peanut particle size distributions&#13;\ndetermined using image analysis. A Rosin-Rammler function was fitted to the&#13;\ncumulative distribution data of each bolus to derive peanut particle size parameters (d50&#13;\nand broadness (b)).&#13;\nResults demonstrated that in heterogeneous food systems the presence of one food&#13;\ncomponent (the matrices) can alter the breakdown of another food component (the&#13;\npeanuts) embedded inside that matrix. The properties of the matrix influenced&#13;\nmastication, the rate of peanut particle size reduction, and the spread of the distribution&#13;\nof peanut particle size inside the matrix, but did not influence the d50 of the peanut&#13;\nparticle size distribution inside the bolus. Peanut properties did not influence&#13;\nmastication, but influenced the d50 of the peanut particle size distribution, the rate of&#13;\nparticle size reduction, and the retention of peanuts in the bolus. It is postulated that the&#13;\nproperties of the matrices largely influence the probability teeth contact peanut particles&#13;\n(known as the selection function), and the properties of the peanuts largely influence&#13;\nparticle fracture per chew (known as the breakage function).