gebhart/patrepeval huggingface dataset:
Determination of the role of conventional, novel and atypical PKC isoforms in the expression of morphine tolerance in mice (2006)

This study comprehensively determines the role of all the major PKC isoforms in the expression morphine tolerance. Pseudosubstrate and receptors for activated C-kinase (RACK) peptides inhibit only a single PKC isoform, while previously tested chemical PKC inhibitors simultaneously inhibit multiple isoforms making it impossible to determine which PKC isoform mediates morphine tolerance. Tolerance can result in a diminished effect during continued exposure to the same amount of substance. In rodents, morphine pellets provide sustained exposures to morphine leading to the development of tolerance by 72 h. We hypothesized that administration of the PKC isoform inhibitors i.c.v. would reverse tolerance and reinstate antinociception in the tail immersion and hot plate tests from the morphine released solely from the pellet. Inhibitors to PKC alpha, gamma and epsilon (100-625 pmol) dose-dependently reinstated antinociception in both tests. The PKC beta(I), beta(II), delta, theta, epsilon, eta and xi inhibitors were inactive (up to 2500 pmol). In other mice, the degree of morphine tolerance was determined by calculating ED50 and potency-ratio values following s.c. morphine administration. Morphine s.c. was 5.6-fold less potent in morphine-pelleted vs. placebo-pelleted mice. Co-administration of s.c. morphine with the inhibitors i.c.v. to either PKC alpha (625 pmol), gamma (100 pmol) or epsilon (400 pmol) completely reversed the tolerance so that s.c. morphine was equally potent in both placebo- and morphine-pelleted mice. The PKC beta(I), beta(II), delta, theta, epsilon, eta and xi inhibitors were inactive. Thus, PKC alpha, gamma and epsilon appear to contribute to the expression of morphine tolerance in mice.
Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells (2013)

This indicates a novel role for G3BP1 in the regulation of cell proliferation in breast cancer cells, perhaps via a regulatory effect on PMP22 expression.
Predictability of Designing Specific Binding Interactions for DNA Minor Groove Ligands from NMR Spectroscopy and Molecular Modeling: A Copper(II)-Activated DNA Cleaver Based on Hoechst 33258 (1995)

Analogs of Hoechst 33258 have been designed and synthesized to incorporate a 3,4-catecholic or a 3,4,5-trihydroxyphenyl function in place of the 4-phenolic group of the template molecule. Molecular design was based on the three-dimensional models of the solution structures of the Hoechst 33258 and its m-hydroxy isomer which had been derived from high-field NMR spectroscopic analysis. The predicted solution structure of the catecholic analog as its minor groove complex with duplex d(CGCGAATTCGCG)2 was confirmed by direct high-resolution NMR spectroscopy combined with molecular dynamics, using NMR-derived distance restraints. While the 3,4-catecholic analog was unable to cleave DNA in the presence of Cu(II) ions, the 3,4,5-trihydroxyphenyl analog of Hoechst 33258 was found to be an effective cleaver of DNA at low concentration when activated by copper(II) ions, a difference ascribed to the inaccessibility for copper chelation of the 3,4-dihydroxy site in its minor groove complex with DNA.
A 155-MHz clock recovery delay- and phase-locked loop (1992)

The authors describe a completely monolithic delay-locked loop (DLL) that may be used either by itself as a deskewing element, or in conjunction with an external voltage-controlled crystal oscillator (VCXO) to form a delay- and phase-locked loop (D/PLL). By phase shifting the input data rather than the clock, the DLL and D/PLL provide jitter-peaking-free clock recovery. Additionally, the jitter transfer function of the D/PLL has a low bandwidth for good jitter filtering without compromising acquisition speed. The D/PLL described here exhibits less than 1 degrees r.m.s. jitter on the recovered clock, independent of the input data density. No jitter peaking is observed over the 40-kHz jitter bandwidth.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Direct haplotyping of chromosomal segments from multiple heterozygotes via allele-specific PCR amplification (1989)

Alele specfic amplcation (ASA) of a DNA segmet [11 Is possible If the polymorphism defining the aleleIb at the 3' end of one of the two prime required for polymerase chain reacon (PCR) [2]. The preseae or absnce of product after amplcaton with a given allele-speciflc primer and an Invariant primer annenag distall tpes the polymorphic priming site. Beyond Its discrimination at the polymorphic site, we hypothesized that ASA would sectively amplf the segment encompassed between primers in either the paternal or maternal chromosome of a heterozygote. Hence, it should be possible to haplotype directly all polymorpbbms nested between PCR primers.
Soft contact: measurement and interpretation of contact angles (2005)

The measurement and interpretation of contact angles deceptively appear to be simple. This paper attempts to summarize the pitfalls in the field, and how to avoid them. First, the fundamental underlying theory that is necessary in order to properly measure and interpret contact angles is discussed, emphasizing recent developments. Then, the practical implications of these theoretical aspects are presented. In addition, the discussion highlights the missing pieces of the picture that need to be completed through future research.
Structural correlates of high antibody affinity: three engineered amino acid substitutions can increase the affinity of an anti-p-azophenylarsonate antibody 200-fold. (1990)

The basis for the 200-fold difference in affinity between two hybridoma antibodies specific for the hapten p-azophenylarsonate (Ars) that have diversified by somatic hypermutation was examined. Oligonucleotide-directed mutagenesis was used to sequentially convert the nucleotide sequence of the lower-affinity antibody into that of the higher-affinity one, and the mutant antibodies generated by transfection of hybridoma cells were analyzed for affinity to Ars-tyrosine. The data showed that out of the 19 amino acid differences between the two hybridoma antibodies, the affinity increase could be reproduced by three heavy-chain substitutions that are present in the high-affinity antibody. The combined effect on affinity of amino acid substitutions was generally found to reflect their individual effects. Although the light chain of the high-affinity antibody did not seem to play a major role in the affinity increase, its contribution varied with the kind and number of heavy-chain substitutions. The results hold promise for antibody engineering and are consistent with a stepwise acquisition of somatic hypermutations in which the existing structural context of an antibody most likely influences the affinity-based selection of later substitutions. They further suggest that many substitutions may be tolerated in vivo during the antigen-driven selection process, even though they confer on the antibody no affinity increase.
[Mechanism of the primary radiobiologic action]. (1998)

Basing on the well-known high sensitivity of the biological processes to alteration of pH of a medium it is assumed that one of the major factors of primary biological effect of ionizing radiation is the increase of acidity in charged particle's tracks. This makes possible to understand the mechanism of protective action of various radioprotectors and the extremal experimental dependence of RBE vs LET has been explained. The position of corresponding maximum was estimated as approximately 10 eV/A in accord with experimental data.
T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases (2014)

Neuroinflammation is involved in several neurodegenerative disorders and emerging evidence indicates that it constitutes a critical process that is required for the progression of neurodegeneration. Microglial activation constitutes a central event in neuroinflammation. Furthermore, microglia can not only be activated with an inflammatory and neurotoxic phenotype (M1-like phenotype), but they also can acquire a neurosupportive functional phenotype (M2-like phenotype) characterised by the production of anti-inflammatory mediators and neurotrophic factors. Importantly, during the past decade, several studies have shown that CD4(+) T-cells infiltrate the central nervous system (CNS) in many neurodegenerative disorders, in which their participation has a critical influence on the outcome of microglial activation and consequent neurodegeneration. In this review, we focus on the analysis of the interplay of the different sub-populations of CD4(+) T-cells infiltrating the CNS and how they participate in regulating the outcome of neuroinflammation and neurodegeneration in the context of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. In this regard, encephalitogenic inflammatory CD4(+) T-cells, such as Th1, Th17, GM-CSF-producer CD4(+) T-cells and γδT-cells, strongly contribute to chronic neuroinflammation, thus perpetuating neurodegenerative processes. In contrast, encephalitogenic or meningeal Tregs and Th2 cells decrease inflammatory functions in microglial cells and promote a neurosupportive microenvironment. Moreover, whereas some neurodegenerative disorders such as multiple sclerosis, Parkinson's disease and Alzheimer's disease involve the participation of inflammatory CD4(+) T-cells 'naturally', the physiopathology of other neurodegenerative diseases, such as amyotrophic lateral sclerosis, is associated with the participation of anti-inflammatory CD4(+) T-cells that delay the neurodegenerative process. Thus, current evidence supports the hypothesis that the involvement of CD4(+) T-cells against CNS antigens constitutes a key component in regulating the progression of the neurodegenerative process.
Migraine and the Hypothalamus (2009)

Migraine is a complex brain disorder where several neuronal pathways and neurotransmitters are involved in the pathophysiology. To search for a specific anatomical or physiological defect in migraine may be futile, but the hypothalamus, with its widespread connections with other parts of the central nervous system and its paramount control of the hypophysis and the autonomic nervous system, is a suspected locus in quo. Several lines of evidence support involvement of this small brain structure in migraine. However, whether it plays a major or minor role is unclear. The most convincing support for a pivotal role so far is the activation of the hypothalamus shown by positron emission tomography (PET) scanning during spontaneous migraine attacks. A well-known theory is that the joint effect of several triggers may cause temporary hypothalamic dysfunction, resulting in a migraine attack. If PET scanning had consistently confirmed hypothalamic activation prior to migraine headache, this hypothesis would have been supported. However, such evidence has not been provided, and the role of the hypothalamus in migraine remains puzzling. This review summarizes and discusses some of the clues.
First evidence supporting a potential role for the BMP/SMAD pathway in the progression of oestrogen receptor‐positive breast cancer (2005)

Oestrogen receptor expression is generally a sign of better tumour differentiation and comparatively good clinical outcome in invasive breast cancer. However, oestrogen receptor-positive, poorly differentiated carcinomas with a poor clinical outcome exist. The underlying genetic mechanisms and the genes involved remain obscure, even though chromosome 7p gains seem to be associated with these uncommon tumours. In this study, we compared two subsets of oestrogen receptor-positive breast cancers, which differed in tumour grade, cytogenetic instability, and tumour proliferation, for their differential gene expression in order to identify proteins involved in the progression of oestrogen receptor-positive breast cancers. We were able to show by means of subtractive suppression hybridization, real-time reverse transcriptase PCR, and tissue microarray analysis that expression of the bone morphogenetic protein receptor IB (BMPR-IB) is a major hallmark of the progression and dedifferentiation of breast cancer. Strong expression of BMPR-IB was associated with high tumour grade, high tumour proliferation, cytogenetic instability, and a poor prognosis in oestrogen receptor-positive carcinomas. Western blot analysis revealed that downstream signalling of this receptor is mainly mediated via phosphorylation of SMAD 1 in oestrogen receptor-positive breast cancer. Even though BMPR-IB was expressed in oestrogen receptor-positive and -negative breast cancers, an impact on tumour grade, proliferation, and cytogenetic instability, as parameters of tumour progression, could only be demonstrated in oestrogen receptor-positive carcinomas. This pro-proliferative effect was complemented by significant anti-apoptotic activity, indicated by XIAP and IAP-2 expression in BMPR-IB-positive carcinomas. These results show that the BMP/SMAD pathway is activated in breast cancer and may contribute to breast cancer progression and dedifferentiation in oestrogen receptor-positive breast cancer. The definition of this pathway characterizes a new potential target in the molecular treatment of invasive breast cancer.
Cyclopropanecarboxylic Acid Esters as Potential Prodrugs with Enhanced Hydrolytic Stability (2008)

Esters of cyclopropanecarboxylic acid demonstrate a substantial increase in stability under both acid- and base-catalyzed hydrolytic conditions. Comparison of the stability of valacyclovir 13 with the cyclopropane analogue 14 shows that at 40 degrees C and pH 6 the half-life of 14 is >300 h while the value for 13 is 69.7 h. CBS-QB3 calculations on isodesmic reactions for transfer of groups from an alkane to an ester show that a cyclopropyl group provides hyperconjugative stabilization.
Etanercept in the treatment of active refractory Crohn's disease: a single-center pilot trial (2001)

Etanercept may be effective in Crohn's disease refractory to standard therapy.
Staff training and development programs (1994)

Abstract Training and development programs directed to staff represent an institutional investment in the skills and careers of nonacademic personnel.
A chopper current-feedback instrumentation amplifier with a 1mHz 1/&#x0192; noise corner and an AC-coupled ripple-reduction loop (2009)

In the precision mechatronics of wafer steppers, thermal expansion is an important source of error. To compensate for this, the temperature of critical mechanical components must be measured with high resolution (≪1µK), typically by using precision thermistor bridges. Furthermore, this resolution must be maintained over several minutes, which means that the amplifier used for bridge readout should have a 1/ƒ noise corner of only a few mHz. Such noise performance is well beyond the capabilities of currently available CMOS amplifiers [1–3].
Life after genetics (2014)

Gene finding is a finite exercise, and a means to an end, rather than an end in itself. The field of human genetics should increasingly shift its attention from disease gene identification to following through on next steps, most importantly pursuing the biological mechanisms underlying genotype-phenotype associations.
History of Regenerative Medicine: Looking Backwards to Move Forwards (2006)

If the song by the international popstar Sting is to be relied upon, 'History will teach us nothing'. At the risk of contradicting a one-time schoolteacher, I believe the reverse is true for regenerative medicine. In fact, I think we dismiss the past at our peril. In this review, I aim to trace the history of regenerative medicine to date. I will examine parallels with other areas of medicine and show how commercial, technical and socio/economic factors have influenced the pace and direction of the sector's evolution. I will discuss how, by learning from the past, those involved in regenerative medicine are reinventing their sector for the better. In conclusion, I will evaluate the current state of the industry, suggest what the future may hold and explain why I believe regenerative medicine is about to 'come of age'.
Two-Wave Nanotherapy To Target the Stroma and Optimize Gemcitabine Delivery To a Human Pancreatic Cancer Model in Mice (2013)

Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance in addition to causing other problems. In order to improve the delivery of gemcitabine, a first-line chemotherapeutic agent, a PEGylated drug-carrying liposome was developed, using a transmembrane ammonium sulfate gradient to encapsulate the protonated drug up to 20% w/w. However, because the liposome was precluded from entering the xenograft site due to the stromal interference, we developed a first-wave nanocarrier that decreases pericyte coverage of the vasculature through interference in the pericyte recruiting TGF-β signaling pathway. This was accomplished using a polyethyleneimine (PEI)/polyethylene glycol (PEG)-coated mesoporous silica nanoparticle (MSNP) for molecular complexation to a small molecule TGF-β inhibitor, LY364947. LY364947 contains a nitrogen atom that attaches, through H-bonding, to PEI amines with a high rate of efficiency. The copolymer coating also facilitates systemic biodistribution and retention at the tumor site. Because of the high loading capacity and pH-dependent LY364947 release from the MSNPs, we achieved rapid entry of IV-injected liposomes and MSNPs at the PDAC tumor site. This two-wave approach provided effective shrinkage of the tumor xenografts beyond 25 days, compared to the treatment with free drug or gemcitabine-loaded liposomes only. Not only does this approach overcome stromal resistance to drug delivery in PDAC, but it also introduces the concept of using a stepwise engineered approach to address a range of biological impediments that interfere in nanocancer therapy in a spectrum of cancers.
Continuous perfusion microfluidic cell culture array for high‐throughput cell‐based assays (2004)

We present for the first time a microfluidic cell culture array for long-term cellular monitoring. The 10 x 10 array could potentially assay 100 different cell-based experiments in parallel. The device was designed to integrate the processes used in typical cell culture experiments on a single self-contained microfluidic system. Major functions include repeated cell growth/passage cycles, reagent introduction, and real-time optical analysis. The single unit of the array consists of a circular microfluidic chamber, multiple narrow perfusion channels surrounding the main chamber, and four ports for fluidic access. Human carcinoma (HeLa) cells were cultured inside the device with continuous perfusion of medium at 37 degrees C. The observed doubling time was 1.4 +/- 0.1 days with a peak cell density of approximately 2.5*10(5) cells/cm(2). Cell assay was demonstrated by monitoring the fluorescence localization of calcein AM from 1 min to 10 days after reagent introduction. Confluent cell cultures were passaged within the microfluidic chambers using trypsin and successfully regrown, suggesting a stable culture environment suitable for continuous operation. The cell culture array could offer a platform for a wide range of assays with applications in drug screening, bioinformatics, and quantitative cell biology.
Retroviral Spread by Induction of Virological Synapses (2004)

Cells of the immune system communicate via the formation of receptor-containing adhesive junctions termed immunological synapses. Recently, retroviruses have been shown to subvert this process in order to pass directly from infected to uninfected immune cells. Such cell-cell viral dissemination appears to function by triggering existing cellular pathways involved in antigen presentation and T-cell communication. This mode of viral spread has important consequences for both the virus and the host cells in terms of viral pathogenesis and viral resistance to immune and therapeutic intervention. This review summarises the current knowledge concerning virological synapses induced by retroviruses.
Crystal Engineering of Novel Cocrystals of a Triazole Drug with 1,4-Dicarboxylic Acids (2003)

Cocrystals of the poorly soluble antifungal drug cis-itraconazole (1) with 1,4-dicarboxylic acids have been prepared. The crystal structure of the succinic acid cocrystal with 1 was determined to be a trimer by single-crystal X-ray. The trimer is comprised of two molecules of 1 oriented in antiparallel fashion to form a pocket with a triazole at either end. The extended succinic acid molecule fills the pocket, bridging the triazole groups through hydrogen-bonding interactions rather than interacting with the more basic piperazine nitrogens. The solubility and dissolution rate of some of the cocrystals are approximately the same as those of the amorphous drug in the commercial formulation and are much higher than those for the crystalline free base. The results suggest that cocrystals of drug molecules have the possibility of achieving the higher oral bioavailability common for amorphous forms of water-insoluble drugs while maintaining the long-term chemical and physical stability that crystal forms provide.
ChemInform Abstract: Rearrangement of 1‐Arylindoles to 5H‐Dibenz(b,f)azepines. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Measurement of arbitrary strain profiles withinfibre gratings (1996)

Results from the first measurement of an arbitrary strain field within a fibre Bragg grating are presented. Low coherence reflectometry has been used, together with a wavelength-tunable reference grating, to obtain strain against distance measurements.
DNA Sequence Recognition by Hybridization to Short Oligomers (1995)

A format 1 technology for performing massive hybridization experiments has been developed as part of the sequencing by hybridization (SBH) project. Arrays of tens of thousands of clones are interrogated with short oligomer probes to determine sets of oligomers that are present in individual clones. SBH requires highly discriminative hybridizations with a large number of probes. One of the main uses of a reconstructed DNA sequence is in a similarity search against databases of known DNA. We argue that sequence reconstruction, even partial, should not be performed for this particular purpose; we provide an information-theoretic proof that the oligomer lists obtained from hybridization experiments should be used directly for similarity searches. We propose a similarity search method that takes full advantage of the subword structure of positively identified oligomers within a clone. The method tolerates error in hybridization experiments, requires fewer probes than necessary for sequencing, and is computationally efficient. To enable direct sequence recognition, we apply the recently developed method of sequence comparison that is based on minimal length encoding and algorithimic mutual information. The method has been tested on both real and simulated data and has led to a correct identification of clones based on hybridizations with 109 short oligomer probes. The method is applicable to hybridization data that comes from both format 1 and format 2 (sequencing chip) hybridization experiments. The sequence recognition method can provide targeting information for large-scale DNA sequencing by gel-based methods or by hybridization.