gebhart/patrepeval huggingface dataset:
Characterization of the Electron Transfer of a Ferrocene Redox Probe and a Histidine-Tagged Hemoprotein Specifically Bound to a Nitrilotriacetic-Terminated Self-Assembled Monolayer (2009)

We report the selective, controlled binding of a model redox probe, 1,1'-bis(N-imidazolylmethyl)ferrocene (Fc-Im2), and a small redox hemoprotein, histidine-tagged recombinant human neuroglobin (hNb), at the surface of metal electrodes (gold and SER-active silver) modified by a self-assembled monolayer (SAM) of a nitrilotriacetic (NTA)-terminated thiol. The resulting SAMs were characterized by cyclic voltammetry and surface-enhanced resonance Raman (SERR) spectroscopy coupled to electrochemistry. Once specifically bounded to the Ni(II)-NTA-modified gold electrode, nearly ideal cyclic voltammetric behavior with relatively fast electron-transfer (ET) communication through the SAM was determined for the Fc-Im2 redox probe. However, no direct electron transfer could be evidenced for the hNb redox protein under the same conditions. This outcome was different from the result obtained during SERR experiments coupled to electrochemistry in which a direct electrochemical conversion of hNb immobilized on a Ni(II)-NTA-modified SER-active Ag electrode was observed. The SERR spectra of the immobilized hNb was the same as the resonance Raman spectra of the protein in homogeneous solution, allowing us to conclude that the native structure of hNb was retained upon immobilization and that the direct ET was not the result of some partial or complete protein denaturation. The long-range ET rate constant (kET) through the SAM was determined by time-resolved SERR spectroscopy. A value of kET=0.12 s(-1) was obtained, which is within the predicted range of a fully nonadiabatic ET through a SAM thickness of approximately 26 A and close to the values previously determined for analogous small redox proteins at similar long-range ET distances. A SERR spectroelectrochemical titration of the immobilized hNb was also carried out, showing both an apparent standard potential (E0') negatively shifted by 100 mV compared with hNb in solution and a gentle slope in the titration curve. These results suggest a range of chemical environments in the surroundings of the redox protein and a variety of interactions with the NTA-terminated SAM. The influence of protein immobilization on E0' is discussed together with the long-range ET rate constant and molecular orientation of the surface-immobilized hNb.
Tumor endothelial marker 8 expression in triple-negative breast cancer. (2011)

TEM8 would appear to represent a new biologic target for designing novel diagnostic or therapeutic approaches for TNBC.
Thiamine biosynthesis in algae is regulated by riboswitches (2007)

In bacteria, many genes involved in the biosynthesis of cofactors such as thiamine pyrophosphate (TPP) are regulated by ribo switches, regions in the 5' end of mRNAs to which the cofactor binds, thereby affecting translation and/or transcription. TPP riboswitches have now been identified in fungi, in which they alter mRNA splicing. Here, we show that addition of thiamine to cultures of the model green alga Chlamydomonas reinhardtii alters splicing of transcripts for the THI4 and THIC genes, encoding the first enzymes of the thiazole and pyrimidine branches of thiamine biosynthesis, respectively, concomitant with an increase in intracellular thiamine and TPP levels. Comparison with Volvox carteri, a related alga, revealed highly conserved regions within introns of these genes. Inspection of the sequences identified TPP riboswitch motifs, and RNA transcribed from the regions binds TPP in vitro. The THI4 riboswitch, but not the promoter region, was found to be necessary and sufficient for thiamine to repress expression of a luciferase-encoding reporter construct in vivo. The pyr1 mutant of C. reinhardtii, which is resistant to the thiamine analogue pyrithiamine, has a mutation in the THI4 riboswitch that prevents the THI4 gene from being repressed by TPP. By the use of these ribo switches, thiamine biosynthesis in C. reinhardtii can be effectively regulated at physiological concentrations of the vitamin.
Cell-cycle dependent antagonistic interactions between paclitaxel and carboplatin in combination therapy (2007)

AbstractThe combination of carboplatin and paclitaxel is widely used to treat multiple solid tumors including ovarian, lung and breast cancer. Usually these drugs are given simultaneously with little regard to the importance of scheduling to obtain a maximal response. To investigate the importance of sequencing, the human breast Bcap37 and ovarian OV2008 cancer cell lines were exposed to carboplatin and paclitaxel in three different sequences: 1) pretreatment with paclitaxel followed by carboplatin; 2) pretreatment of carboplatin followed by paclitaxel and 3) simultaneous treatment with these two agents. The combination of carboplatin and paclitaxel resulted in antagonistic interactions when tumor cells were exposed to carboplatin prior to paclitaxel or exposed to the two drugs simultaneously, but there was little antagonistic interaction observed when paclitaxel was administered before carboplatin. Biochemical examination revealed that pretreatment or cotreatment of carboplatin inhibited paclitaxel-induced IκBα degradation and bcl-2 phosphorylation. Further analyses demonstrated that carboplatin could significantly interfere with the cytotoxic effects of paclitaxel on both mitotic arrest and apoptotic cell death unless paclitaxel was administered before carboplatin. These results indicate that the interaction between paclitaxel and carboplatin is highly schedule dependent. The optimal schedule for this combination is sequential exposure of paclitaxel followed by carboplatin.
Sulfatide promotes the folding of proinsulin, preserves insulin crystals, and mediates its monomerization (2001)

Sulfatide is a glycolipid that has been associated with insulin-dependent diabetes mellitus. It is present in the islets of Langerhans and follows the same intracellular route as insulin. However, the role of sulfatide in the beta cell has been unclear. Here we present evidence suggesting that sulfatide promotes the folding of reduced proinsulin, indicating that sulfatide possesses molecular chaperone activity. Sulfatide associates with insulin by binding to the insulin domain A8--A10 and most likely by interacting with the hydrophobic side chains of the dimer-forming part of the insulin B-chain. Sulfatide has a dual effect on insulin. It substantially reduces deterioration of insulin hexamer crystals at pH 5.5, conferring stability comparable to those in beta cell granules. Sulfatide also mediates the conversion of insulin hexamers to the biological active monomers at neutral pH, the pH at the beta-cell surface. Finally, we report that inhibition of sulfatide synthesis with chloroquine and fumonisine B1 leads to inhibition of insulin granule formation in vivo. Our observations suggest that sulfatide plays a key role in the folding of proinsulin, in the maintenance of insulin structure, and in the monomerization process.
Redox Imbalance, Macrocytosis, and RBC Homeostasis (2006)

The erythrocyte represents a major component of the antioxidant capacity of the blood through the enzymes contained in the cell, the glutathione system, and the low-molecular-weight antioxidants of the erythrocyte membrane. A further major red blood cell contribution is in regenerating consumed redox equivalents via the oxidative pentose phosphate pathway and glutathione reductase. Moreover, its extracellular antioxidant capacity, its mobility, and the existence of reducing equivalents far in excess of its normal requirements make erythrocytes function as an effective oxidative sink in the organism. That is why red blood cell metabolism and homeostasis strongly affect the antioxidant properties of the whole body. Conversely, the relation between macrocytosis and oxidative stress has not been fully delineated. Reviewing the mechanisms involved in red blood cell homeostasis in cases of redox imbalance is crucial in identification of factors that could potentially improve erythrocyte survival and defense against oxidant damage.
Sequence analysis of the polymerase 1 gene and the secondary structure prediction of polymerase 1 protein of human influenza virus A/WSN/33 (1982)

The nucleotide sequence of polymerase 1 (P1) gene of a human influenza virus (A/WSN/33) has been determined by using cDNA clones, except for the last 83 nucleotides, which were obtained by primer extension. The WSN P1 gene contains 2,341 nucleotides and codes for a protein of 757 amino acids (Mr = 86,500). P1 gene possesses a striking tandem repeat of 12 nucleotides (nucleotide position 2,188 to 2,199, 2,200 to 2,211) and a corresponding tandem repeat of tetrapeptide in the P1 protein. The deduced sequence of P1 protein is enriched in basic amino acids, particularly arginine. In addition, it also contains clusters of basic amino acids which may provide sites for the interaction with the template virion RNA capped primer as well as with other proteins involved in viral replication and transcription. A secondary structure prediction, using Chou and Fasman analyses (Annu. Rev. Biochem. 47:251-276, 1978), shows that the P1 protein possesses some unique features, viz., one "four-helical supersecondary structure" and four "polypeptide double helices" (antiparallel beta-pleated sheets) which are considered important in RNA binding.
Decay-Accelerating Factor Deficiency Increases Susceptibility to Dextran Sulfate Sodium-Induced Colitis: Role for Complement in Inflammatory Bowel Disease (2004)

Decay-accelerating factor (DAF or CD55) is expressed on colonic epithelial cells but its function in the mucosa is unknown. In humans, a proportion of DAF-deficient (Cromer INAB) patients develop inflammatory bowel disease (IBD). To evaluate how DAF deficiency may contribute to gut inflammation and thus could play a role in IBD pathogenesis, we compared the severity of dextran sulfate sodium-induced colitis in Daf1 gene-targeted and control mice. Seven days after consuming 3% dextran sulfate sodium in their drinking water, Daf1(-/-) mice suffered markedly greater weight loss (-24.7 +/- 7.5% vs -14.2% +/- 4.9%), exhibited uniformly bloody diarrhea as compared with soft stool in control mice, developed shortened colons, and had larger spleens. Histological examination of distal colons showed massively increased neutrophilic and mononuclear cell infiltration, greater epithelial cell destruction, and increased ulcerations. Cytokine production in organ cultures of colonic explants showed increased levels of IL-12 and IL-6. Fourteen days after switching back to regular water, in contrast to the Daf1(+/+) controls which showed little stool abnormality, all Daf1(-/-) mice continued to have diarrhea. Organ culture cytokine measurements at this time point, i.e., the end of the recovery phase, showed markedly increased levels of IL-10 (6-fold), IL-12 (4-fold), and IL-6 (2-fold), as well as TNF-alpha (>10-fold) compared with the controls. Our findings argue that, as shown for IL-10 in IL-10(-/-) mice and IL-2 in IL-2(-/-) mice, DAF control of complement additionally is important in regulating gut homeostasis and consequently its activity may participate in protecting against IBD.
Cell envelope proteins of Staphylococcus epidermidis grown in vivo in a peritoneal chamber implant (1992)

Staphylococcus epidermidis was grown in vivo in chambers implanted intraperitoneally in rats. The cell wall and cytoplasmic membrane protein profiles of the in vivo-grown organisms were compared with those of S. epidermidis grown in vitro in nutrient broth (NB), in iron-restricted NB, or in pooled human peritoneal dialysate (HPD). Compared with growth in broth and in common with growth in HPD, growth in vivo in chambers resulted in the repression of many S. epidermidis wall proteins, with proteins of 27, 42, 54, and 70 kDa predominating. Growth in vivo also resulted in the induction of two iron-repressible cytoplasmic membrane proteins of 32 and 36 kDa, which were also present in staphylococci grown in HPD and in iron-restricted NB. Immunoblotting experiments revealed that in sera taken 21 days after inoculation of the intraperitoneal chambers, the predominant antibody response to cell envelope proteins was directed against the 32- and 36-kDa iron-repressible membrane proteins.
Multigrating method for flattened spectral responsewavelength multi/demultiplexer (1997)

The authors successfully demonstrate a new method, called a multigrating method, for a flattened spectral response. It uses one-focal-point couplers and several interleaved monomode waveguide gratings. It has a bandwidth of 0.94 nm at –1 dB and of 1.8 nm at –20 dB. The loss penalty due to channel flattening is only 2.2 dB.
The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans. (1994)

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.
PARP1-Driven Poly-ADP-Ribosylation Regulates BRCA1 Function in Homologous Recombination–Mediated DNA Repair (2014)

We propose a model that describes how BRCA1 functions to both support and restrict HRR. BRCA1 PARsylation is a key event in this process, failure of which triggers hyper-recombination and chromosome instability. Thus, hyperfunctioning BRCA1 can elicit genomic abnormalities similar to those observed in the absence of certain BRCA1 functions.
Epinephrine for the treatment of anaphylaxis: do all 40 mg sublingual epinephrine tablet formulations with similar in vitro characteristics have the same bioavailability? (2006)

Epinephrine autoinjectors are underutilized in the first aid emergency treatment of anaphylaxis in the community; so non-invasive sublingual epinephrine administration is being proposed. In order to determine the effect of changing excipients on the bioavailability of sublingual epinephrine, four distinct fast-disintegrating epinephrine 40 mg tablet formulations, A, B, C and D, were manufactured using direct compression. All formulations were evaluated for tablet hardness (H), disintegration time (DT) and wetting time (WT). In a prospective 5-way crossover study, four sublingual formulations and epinephrine 0.3 mg i.m. as a control were tested sequentially in a validated rabbit model. Blood samples were collected before dosing and at intervals afterwards. Epinephrine plasma concentrations were measured using HPLC-EC. All tablet formulations met USP standards for weight variation and content uniformity, and resulted in similar mean H, DT and WT (n=6). The area under the curve (AUC), maximum concentration (C(max)) and time at which C(max) was achieved (T(max)) did not differ significantly after the sublingual administration of formulation A and epinephrine 0.3 mg i.m. The AUC after B, C and D were significantly lower (p<0.05) than after epinephrine 0.3 mg i.m. These results suggest that the selection of excipients used in these tablet formulations can affect the bioavailability of sublingually administered epinephrine.
Resonant frequency tunableness of solidly mounted resonators (2010)

The performance of solidly mounted resonator (SMR) depends on the thickness control of each layer. Since thickness variation is inevitable in film deposition, the resonant frequency will shift from the desired value. In order to calculate the required electrode thickness for a given resonant frequency, an SMR is treated as a combination of two substructures, the top electrode and the remaining layers. The substructure synthesis method is employed to calculate the required thickness of electrode. Monte Carlo simulation is adopted to investigate tunableness of resonant frequency with random thickness deviation in every layer. An SMR with a 6-period-reflector and 2.4GHz series resonant frequency is chosen for the investigation. The material of piezoelectric layer is aluminum nitride and the reflector is composed of tungsten and aluminum films. The top electrode is a half-wavelength Al film and the SMR is mounted on a silicon substrate of 525μm in thickness. Monte Carlo simulation shows that the 3σ of electrode trimming value is 0.03μm when the layer thickness deviation with 3σ value equals to 1% of the mean thickness.
Biosafety Features of Lentiviral Vectors (2013)

Over the past decades, lentiviral vectors have evolved as a benchmark tool for stable gene transfer into cells with a high replicative potential. Their relatively flexible genome and ability to transduce many forms of nondividing cells, combined with the potential for cell-specific pseudotyping, provides a rich resource for numerous applications in experimental platforms and therapeutic settings. Here, we give an overview of important biosafety features of lentiviral vectors, with detailed discussion of (i) the principles of the lentiviral split-genome design used for the construction of packaging cells; (ii) the relevance of modifications introduced into the lentiviral long terminal repeat (deletion of enhancer/promoter sequences and introduction of insulators); (iii) the basic features of mRNA processing, including the Rev/Rev-responsive element (RRE) interaction and the modifications of the 3' untranslated region of lentiviral vectors with various post-transcriptional regulatory elements affecting transcriptional termination, polyadenylation, and differentiation-specific degradation of mRNA; and (iv) the characteristic integration pattern with the associated risk of transcriptional interference with cellular genes. We conclude with considerations regarding the importance of cell targeting via envelope modifications. Along this course, we address canonical biosafety issues encountered with any type of viral vector: the risks of shedding, mobilization, germline transmission, immunogenicity, and insertional mutagenesis.
Advances in Glaucoma Treatment and Management: Outflow Drugs (2012)

I ntraocular pressure (IOP) rises when the balance between aqueous humor formation and outflow resistance is compromised. In a normal eye, ciliary muscle (CM) and trabecular meshwork (TM) contraction and relaxation function in synchrony to provide fine control of outflow. Recent investigations of the role of endothelial nitric oxide synthase (eNOS) 1 suggest TM mechanosensitivity as a homeostatic mechanism mediated in part by NO to maintain normal outflow facility and IOP. The active role of TM contraction and relaxation in the regulation of IOP is also likely to be mediated in part by the actomyosin contractility/cytoskeleton/cell-cell and cell-matrix adhesion system. The cytoskeleton and contractility mechanisms may be the efferent "execution" arm of the reflexive and regulatory mechanism; their arrangement governs the final facility. The eNOS/NO system appears to be a signal/transduction arm that mediates response to the stressors. It is generally agreed that the greatest resistance to outflow resides in the juxtacanalicular region and inner wall of Schlemm's canal (SC)-areas that are directly affected by contractile changes in the CM and TM. The interactions of this system are just now being appreciated. Understanding how this system functions is critical for determining how to effectively and efficiently manipulate elements of the system to therapeutic effect. The molecular pathways that modulate uveoscleral and trabecular outflow are complex. Advances in identifying the most salient therapeutic elements in such complicated systems are best catalyzed in small, focused meetings. These are a valuable complement to the larger research meetings, and more are needed.
Theory of Electromagnetic Time-Reversal Mirrors (2010)

The theory of monochromatic time-reversal mirrors (TRM) or equivalently phase conjugate mirrors is developed for electromagnetic waves. We start from the fundamental time-symmetry of the Maxwell's equations. From this symmetry, a differential expression similar to the Lorentz reciprocity theorem is deduced. The radiating conditions on TRM are expressed in terms of 6-dimension Green's functions. To predict the time reversal focusing on antenna arrays, a formalism that involves impedance matrix is developed. We show that antenna coupling can dramatically modify the focal spot. Especially, we observe, that in some circumstances, sub-wavelength focusing on a bi-dimensional array may arise.
Manganism and idiopathic parkinsonism (1994)

From the comparison we have made between PD and manganism, we draw the following conclusions: 1. There are similarities between PD and manganism, notably the presence of (a) generalized bradykinesia and (b) widespread rigidity. 2. There are also dissimilarities between PD and manganism, notably the following in manganism: (a) less-frequent resting tremor, (b) more frequent dystonia, (c) a particular propensity to fall backward, (d) failure to achieve a sustained therapeutic response to levodopa, and (e) failure to detect a reduction in fluorodopa uptake by PET. Further studies are likely to yield more discriminants between PD and manganism. For example, PET with raclopride may be useful in early cases of manganism, and MRI may be helpful in patients with advanced manganism.
MiR‐940 inhibits hepatocellular carcinoma growth and correlates with prognosis of hepatocellular carcinoma patients (2015)

Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death in China. Deregulation of microRNA (miRNA) contributes to HCC development by influencing cell growth, apoptosis, migration or invasion. It has been proved that miR-940 plays important roles in various cancers. Here we investigated the role of miR-940 in HCC. We found that miR-940 was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-940 expression in HCC tissues significantly correlated with the reduced patient's survival rate. Overexpression of miR-940 inhibited HCC cell line growth and induced cell apoptosis, and vice versa. Estrogen-related receptor gamma (ESRRG) was targeted by miR-940, and suppression of ESRRG inhibited HCC cell lines growth and induced cell apoptosis. In conclusion, we found that a lower level of miR-940 in HCC promoted cellular proliferation via ESRRG, which may lead to the short survival period of HCC patients.