gebhart/patrepeval huggingface dataset:
Phase equilibria in copolymer/homopolymer ternary blends: Molecular weight effects (1990)

The phase behavior of ternary blends of an A–B random copolymer with two homopolymers (A and B) is investigated within the Flory–Huggins lattice theory. We restrict consideration to the formation of (isotropic) liquid phases. For compositionally symmetric systems in which the two homopolymers have equal molecular weights, two different topologies are found for the phase diagrams according to the length of the copolymer relative to the homopolymers. Namely, upon lowering the temperature, a three-liquid-phase region emerges either continuously via a tricritical point if the copolymer is long enough, or discontinuously otherwise. This change in phase behavior, an entropy of mixing effect, occurs when the copolymer length is a fraction 2/5 of the homopolymer molecular weight. The properties of the (symmetric) tricritical points are discussed, as well as the phase behavior of systems in which the copolymer is not symmetrical in composition and/or the two homopolymers differ in size. This Flory–Huggins approach should be valid for blends containing random copolymers, but also, at high enough temperatures, for blends that contain block copolymers, the temperature range of validity being broader for smaller block copolymers. The critical behavior of systems containing block copolymers is described by the simple Flory–Huggins theory over a range delineated by isotropic Lifshitz points. These Lifshitz points are located within the random phase approximation.
Changes in the ratio of type-I and type-II collagen expression during monolayer culture of human chondrocytes (2004)

We compared the changes in the ratio of type-I and type-II collagen in monolayer cultures of human articular chondrocytes (HAC). HAC were isolated from samples of cartilage from normal joints and cultivated in monolayer for up to 46 days. Expression of collagen type-I and type-II was determined by immunocytochemistry, Western blotting, and the nested reverse transcription polymerase chain reaction (RT-PCR), and quantified by real-time PCR. The transition from a spherical morphology to the flattened morphology of an anchorage-dependent culture was accompanied by a rapid change in the collagen phenotype with the replacement of collagen type II by collagen type I. This was confirmed by immunocytochemistry and Western blotting between days 21 and 28. Using techniques for the analysis of gene transcription (nested RT-PCR and real-time PCR), a complete switch of collagen gene expression was not observed. Expression of collagen type I increased 100-fold during the culture time. That of collagen type II was found during the entire period and decreased more than 100-fold. The main finding was that expression of the genes encoding collagen type I and II was highly time-dependent and the ratio of collagen type II to I (CII/CI), defined as an index of cell differentiation, was significantly higher (215- to 480-fold) at the beginning of the culture. At the end of the experimental culture time, ratios between 0.1 and 1 were reached.
The Cauchy Problem for a Forced Harmonic Oscillator (2007)

We construct an explicit solution of the Cauchy initial value problem for the one-dimensional Schroedinger equation with a time-dependent Hamiltonian operator for the forced harmonic oscillator. The corresponding Green function (propagator) is derived with the help of the generalized Fourier transform and a relation with representations of the Heisenberg-Weyl group N(3) in a certain special case first, and then is extended to the general case. A three parameter extension of the classical Fourier integral is discussed as a by-product. Motion of a particle with a spin in uniform perpendicular magnetic and electric fields is considered as an application; a transition amplitude between Landau levels is evaluated in terms of Charlier polynomials. In addition, we also solve an initial value problem to a similar diffusion-type equation.
Strained Si and Ge MOSFETs with high-k/metal gate stack for high mobility dual channel CMOS (2006)

Epitaxial strained Si and Ge n- and p-MOSFETs with a TiN/HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2 </sub> gate stack were fabricated with the same process for a dual channel integration scheme. Compared to the HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> /Si reference, X1.7 strained Si electron and X9 strained Ge hole mobility gains are demonstrated, achieving symmetric n- and p-MOSFET I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Dsat </sub> performance. This X9 strained Ge hole mobility enhancement highly exceeds previous reported results on Ge pMOSFETs with high-k dielectrics. For the first time, such a hole mobility enhancement, theoretically predicted and experimentally reported with thick SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2 </sub> gate dielectrics, is demonstrated with a thin high-k gate dielectric (EOT=14Aring)
Interleukin-2 (IL-2) Regulates the Accessibility of the IL-2-Responsive Enhancer in the IL-2 Receptor α Gene to Transcription Factors (1999)

Interleukin-2 (IL-2) responsiveness of T lymphocytes is controlled through transcription of the IL-2 receptor (IL-2R) alpha subunit by antigen and by IL-2 itself. IL-2 induces IL-2Ralpha transcription via an IL-2-responsive enhancer (IL-2rE), whose activity depends on the cooperative binding of IL-2-induced STAT5 to two sites and of constitutively active Elf-1 to a third one. Here we describe the changes in IL-2rE chromatin that occur in normal T lymphocytes upon activation of IL-2Ralpha expression. In cells induced to transiently express IL-2Ralpha with concanavalin A (which mimics antigen), none of the IL-2rE sites is occupied despite the presence of Elf-1 and STAT1, which bind to the IL-2rE in vitro. The two STAT binding sites are occupied rapidly upon IL-2 stimulation, concomitantly with STAT5 activation. Occupation of the Elf-1 binding site is delayed, although Elf-1 concentration and binding activity are not modified by IL-2. Digestion of T-cell chromatin with DNase I and micrococcal nuclease shows that IL-2 induces the appearance of nuclease-hypersensitive sites flanking the IL-2rE. Thus IL-2, in addition to activating STAT5, appears to regulate IL-2Ralpha transcription by making IL-2Ralpha chromatin accessible to transcription factors.
Analysis of the role of 5' and 3' flanking sequence elements upon in vivo expression of the plant tRNATrp genes. (1995)

We have isolated the majority (seven) of the tRNA(Trp) genes of Arabidopsis and have studied the 5' and 3' flanking sequence requirements for their efficient expression in vivo by using an assay requiring translational suppression of the luciferase reporter gene. The expressed tRNA(Trp) genes contain no highly conserved 5' flanking sequences; however, these sequences are distinctly AT rich, contain several possible TATA elements, and are bound in vitro by recombinant plant TATA binding protein. Replacement of the natural 5' flanking sequences with three different sequences lacking TATA elements reduced expression in vivo up to 10-fold; the same effect was observed when the TATA elements of the natural 5' sequences were inactivated by point mutations. Introduction of a single TATA element from the adenovirus major late promoter into an artificial 5' flanking region of the tRNA(Trp) gene enhanced expression in vivo when the TATA element was placed at position -32 relative to the first nucleotide of the mature tRNA sequence, but not when it was placed at position -24. Primer extension analyses of in vitro transcripts revealed that the position of the TATA element helps dictate the start site of transcription. Efficient expression of the tRNA genes in vivo also required 3' flanking sequences capable of terminating transcription.
Discovery of β-Arrestin Biased Ligands of 5-HT 7 R (2018)

Though many studies have been published about therapeutic potentials of selective 5-HT<sub>7</sub>R ligands, there have been few biased ligands of 5-HT<sub>7</sub>R. The development of potent and selective biased ligands of 5-HT<sub>7</sub>R would be of great help in understanding the relationship between pharmacological effects and G protein/β-arrestin signaling pathways of 5-HT<sub>7</sub>R. In order to identify 5-HT<sub>7</sub>R ligands with biased agonism, we designed and synthesized a series of tetrahydroazepine derivatives 1 and 2 with arylpyrazolo moiety or arylisoxazolo moiety. Through several biological evaluations such as binding affinity, selectivity profile, and functions in G protein and β-arrestin signaling pathways, 3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[3,4- d]azepine 1g was discovered as the β-arrestin biased ligand of 5-HT<sub>7</sub>R. In an electroencephalogram (EEG) test, 1g increased total non-rapid eye movement (NREM) sleep time and decreased total rapid eye movement (REM) sleep time.
Reduction of Unsaturated Aliphatic Mono-and Dicarboxylic Acids and Brominated Aliphatic Acids with Raney Alloys in an Alkaline Solution, Affording the Corresponding Saturated Aliphatic Acids (1988)

The reduction of trans-2-pentenoic acid (1a), 4-pentynoic acid (5), and 2-bromopentanoic acid (6) with Ni-Al and Cu-Al alloys in 10% NaOH solution afforded the expected pentanoic acid (4) in good yields. Under the above conditions, trans-3-and 4-pentenoic acids, (2) and (3), were not reduced. But, the reduction in the presence of 10% Pd/C catalyst (43 weight % of the alloys) gave 4. In 10% Na_2CO_3 solution, the treatment of 5 with Cu-Al afforded pen-tenoic acid (3) as a major product. The reduction of 2,3-dibromopentanoic acid (8) gave 4 or a mixture of 4, la, and cis-2-pentenoic acid (1b) upon the conditions employed. Fumaric acid (10), maleic anhydride (11), and acety-lenedicarboxylic acid (12), and 2,3-dibromosuccinic acid (13) afforded the expected succinic acid (14) in 71-80%yields in the reduction with the alloys in 10% NaOH solution.
Exosome mimetics: a novel class of drug delivery systems (2012)

The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics.
Transformation of Tetrahymena to cycloheximide resistance with a ribosomal protein gene through sequence replacement. (1991)

A method for transforming Tetrahymena has been established earlier, but its application has been limited because of the lack of selectable markers other than the rRNA-encoding DNA (rDNA). Mutations in the yeast ribosomal protein L29 gene (CYH2) are known that confer cycloheximide resistance. We have cloned and sequenced the homologue of this gene from both a wild-type and a cycloheximide-resistant (ChxA) strain of Tetrahymena. Surprisingly, a comparison shows that the ChxA mutation is not present in the CYH2 homologue. We therefore created the yeast mutations in the Tetrahymena gene by site-directed mutagenesis and used them to transform Tetrahymena either with or without linking to an rDNA vector. All clones transformed by the rDNA vector also became resistant to cycloheximide when the rDNA contained the engineered mutant genes. Without the rDNA vector, the mutant genes transform approximately 1% of injected cells to become resistant to cycloheximide. DNA analysis indicates that transformation occurs by replacement of the host sequence and not by random integration of the injected sequence. The replacement occurs to some but not all copies of this gene in the polyploid macronuclear genome. Thus, transformation in Tetrahymena occurs by specific sequence replacement, and the injected mutant genes can serve as dominant selectable transformation markers in this organism.
<title>Development of a sensitive detection system based on the photothermal effect for biomolecular interaction studies</title> (1996)

THe use of a photothermal detection system for the study of interacting biomolecules is described. Two different setups are presented to demonstrate the performance of the system by measurements of DNA/intercalator-samples immobilized on membrane supports used in molecular biological techniques.
Dexmedetomidine: sedation, analgesia and beyond (2008)

Dexmedetomidine is a novel agent with a wide safety margin and excellent sedative and moderate analgesic properties. Though its broadest use is currently in surgical and nonsurgical intensive care unit patients, dexmedetomidine appears to have promising future applications in the areas of neuroprotection, cardioprotection and renoprotection.
Differential responses of oligodendrocytes to tumor necrosis factor and other pro-apoptotic agents: Role of ceramide in apoptosis (1999)

Staurosporine induced apoptosis in a human oligodendroglioma cell line (HOG), neonatal rat oligodendrocyte (O2A(+)) precursors, and mature rat oligodendrocytes. In all three cell culture systems, the activation of caspase-3-like activity (CPP32) coincided with the increased formation of ceramide from sphingomyelin and the onset of DNA fragmentation. Further, the addition of exogenous C(2)-ceramide induced CPP32 activation and DNA fragmentation in all three culture systems. Raising endogenous ceramide levels by the addition of the ceramidase inhibitor, oleoylethanolamine, enhanced apoptosis in both a time- and concentration-dependent manner. Inhibitors of phosphatidylinositol 3-kinase (wortmannin and LY294002) also induced caspase-3 (CPP32) activation, increased ceramide formation, induced DNA fragmentation, and reduced cell viability. In contrast, cytokines such as tumor necrosis factor-alpha (TNF-alpha) had a differential effect on the three cell cultures. Thus, TNF-alpha (160 ng/ml) induced 70% apoptosis in 24 hr in freshly isolated rat brain O2A(+) precursor cells, 60% apoptosis in 24 hr in a human oligodendroglioma (HOG) cell line, but no apoptosis in mature neonatal rat oligodendrocytes. Interferon-gamma augmented the activation of CPP32 by TNF-alpha in HOG cells and O2A(+) oligodendrocyte precursor cells but had no effect on mature oligodendrocytes. Thus, the death pathway appears to be similar in the three cell lines but the lack of coupling between TNF-alpha receptors and the apoptotic pathway leads to a lack of response to cytokines in mature oligodendrocytes.
A Protein Reacted with Anti-vitronectin Antibody Accumulates in Tumors Derived from B16F10 Melanoma Cells. (1998)

Vitronectin is a cell-adhesive glycoprotein in blood plasma and extracellular matrix. We have examined the participation of vitronectin in experimental metastasis of B16F10 mouse melanoma cells which metastasized to lung. By Western blotting, a protein reacted with anti-rat vitronectin antibody was found to be enriched more in the melanoma parenchyma in the lung than the sum of cultured melanoma cells and normal lung tissue. The protein was similarly abundant in tumors of B16F10 cells grown subcutaneously in mice. By immunofluorescence of the tissues, the signal detected with anti-rat vitronectin was found to be localized at nuclei in melanoma cells metastasized in the lung as well as in tumors just grown subcutaneously. These results indicate that the protein reacted with anti-vitronectin antibody is expressed much more in the growing mass of B16F10 melanoma cells in vivo than in vitro.
Joint detection with low computational complexity for hybrid TD-CDMA systems (1999)

In the hybrid multiple access technique TD/CDMA both multiple-access interference (MAI) and intersymbol interference (ISI) arise. In order to combat the overall interference (ISI+MAI), we propose two efficient joint detection schemes based respectively on zero-forcing and minimum-mean square error criteria. If M denotes the product of the number of active users U and the number of symbols per block N, the computational complexity has been reduced from O(M/sup 3/), of previously proposed schemes, to O(MU/sup 2/), where U/spl Lt/M. In fact, exploiting the asymptotic equivalence between finite-order Toeplitz matrices and circulant matrices, most computation can be carried out very efficiently through an extensive use of DFT and IDFT transforms. Performance results based on the UMTS standard under definition are presented.
Late-onset pericardial tamponade, bilateral pleural effusions and recurrent immune monoarthritis induced by ipilimumab use for metastatic melanoma (2016)

While an important agent in the contemporary anti-melanoma armamentarium, ipilimumab is associated with serious immune reactions including late immune-mediated side effects. Recently, a case of late-onset acute pericarditis with tamponade was reported at 12 weeks after the last dose of ipilimumab. While polyarthralgia rheumatica has been previously documented with ipilimumab, we were not able to find any reports of recurrent monoarthritis with the use of this agent. Therefore, we present herein a unique case featuring a patient with late-onset autoimmune pleuropericarditis leading to cardiac tamponade at 24 weeks post-ipilimumab and recurrent late immune knee arthritis at 8 and 32 weeks, respectively. Furthermore, this late-onset toxicity seen with ipilimumab might also be expected with the PD1 inhibitors currently in clinical use. Timely diagnosis and prompt steroid use are crucial to ensure favorable clinical outcomes in these patients.
Strategies for Enhancing Vaccine-Induced CTL Antitumor Immune Responses (2012)

Vaccine-induced cytotoxic T lymphocytes (CTLs) play a critical role in adaptive immunity against cancers. An important goal of current vaccine research is to induce durable and long-lasting functional CTLs that can mediate cytotoxic effects on tumor cells. To attain this goal, there are four distinct steps that must be achieved. To initiate a vaccine-induced CTL antitumor immune response, dendritic cells (DCs) must capture antigens derived from exogenous tumor vaccines in vivo or autologous DCs directly loaded in vitro with tumor antigens must be injected. Next, tumor-antigen-loaded DCs must activate CTLs in lymphoid organs. Subsequently, activated CTLs must enter the tumor microenvironment to perform their functions, at which point a variety of negative regulatory signals suppress the immune response. Finally, CTL-mediated cytotoxic effects must overcome the tolerance induced by tumor cells. Each step is a complex process that may be impeded in many ways. However, if these steps happen under appropriate regulation, the vaccine-induced CTL antitumor immune response will be more successful. For this reason, we should gain a better understanding of the basic mechanisms that govern the immune response. This paper, based on the steps necessary to induce an immune response, discusses current strategies for enhancing vaccine-induced CTL antitumor immune responses.
Hybrid Polymer–Lipid Films as Platforms for Directed Membrane Protein Insertion (2015)

Hybrids composed of amphiphilic block copolymers and lipids constitute a new generation of biological membrane-inspired materials. Hybrid membranes resulting from self-assembly of lipids and polymers represent adjustable models for interactions between artificial and natural membranes, which are of key importance, e.g., when developing systems for drug delivery. By combining poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) amphiphilic copolymers (PDMS-b-PMOXA) with various phospholipids, we obtained hybrid films with modulated properties and topology, based on phase separation, and the formation of distinct domains. By understanding the factors driving the phase separation in these hybrid lipid-polymer films, we were able to use them as platforms for directed insertion of membrane proteins. Tuning the composition of the polymer-lipids mixtures favored successful insertion of membrane proteins with desired topological distributions (in polymer or/and lipid regions). Controlled insertion and location of membrane proteins in hybrid films make these hybrids ideal candidates for numerous applications where specific spatial functionality is required.
Combination therapies for multiple sclerosis: scientific rationale, clinical trials, and clinical practice (2007)

More effective therapies are needed to treat multiple sclerosis. There are good scientific rationales for the use of combination therapy in multiple sclerosis, and the pharmacologic principles for evaluating and understanding their actions are available. The evaluation of specific combination therapies in the controlled setting of clinical trials should be a priority in clinical multiple sclerosis research.
The Preparation of Optically Pure 3-Hydroxyalkanoic Acid. The Enantioface-differentiating Hydrogenation of the C=O Double Bond with Modified Raney Nickel. XXXVII. (1982)

Abstract The enantioface-differentiating hydrogenation of methyl 3-oxoalkanoate (CH3(CH2)nCOCH2COOCH3, n=0, 6, 8, 10, 12) over the (R,R)-tartaric acid–NaBr–modified Raney nickel catalyst ((R,R)-TA–NaBr–MRNi) gave methyl (R)-3-hydroxyalkanoate (CH3(CH2)nCH(OH)CH2COOCH3, n=0, 6, 8, 10, 12) in an average optical yield of 85%. After the methyl ester had been converted to dicyclohexylammonium salt of 3-hydroxyalkanoic acid, the salt was recrystallized three times from acetonitrile and then treated with acid to give optically pure (R)-3-hydroxyalkanoic acid (CH3(CH2)nCH(OH)CH2COOH, n=0, 6, 8, 10, 12) in a reasonable yield. From the hydrogenation product with (S,S)-TA–NaBr–MRNi, optically pure (S)-3-hydroxyalkanoic acid was obtained by the same process as above.
Mannosidase I inhibition rescues the human α-sarcoglycan R77C recurrent mutation (2008)

Limb girdle muscular dystrophy type 2D (LGMD2D, OMIM600119) is a genetic progressive myopathy that is caused by mutations in the human alpha-sarcoglycan gene (SGCA). Here, we have introduced in mice the most prevalent LGMD2D mutation, R77C. It should be noted that the natural murine residue at this position is a histidine. The model is, therefore, referred as Sgca(H77C/H77C). Unexpectedly, we observed an absence of LGMD2D-like phenotype at histological or physiological level. Using a heterologous cellular model of the sarcoglycan complex formation, we showed that the R77C allele encodes a protein that fails to be delivered to its proper cellular localization in the plasma membrane, and consequently to the disappearance of a positively charged residue. Subsequently, we transferred an AAV vector coding for the human R77C protein in the muscle of Sgca-null mice and were able to pharmacologically rescue the R77C protein from endoplasmic reticulum-retention using proteasome or mannosidase I inhibitors. This suggests a therapeutic approach for LGMD2D patients carrying mutations that impair alpha-sarcoglycan trafficking.