gebhart/patrepeval huggingface dataset:
Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors (2008)

Despite the use of the sirolimus (rapamycin) drug-eluting coronary stent, diabetics are at increased risk of developing in-stent restenosis for unclear reasons. Hyperleptinemia, which often coexists with diabetes and metabolic syndrome, is an independent risk factor for progression of coronary artery disease. It has not been determined whether elevated circulating leptin decreases the efficacy of the sirolimus drug-eluting stent in inhibiting neointimal hyperplasia, the process underlying restenosis after stenting. Here we show that leptin activates the mammalian target of rapamycin (mTOR) signaling pathway in primary murine vascular smooth muscle cells (VSMC) and stimulates VSMC proliferation in a PI3K-dependent fashion. Exogenous leptin, administered at levels comparable to those found in obese humans, promotes neointimal VSMC hyperplasia in a murine femoral artery wire injury model. Leptin significantly increases the dose of the mTOR inhibitor sirolimus that is required for effective inhibition of neointimal formation. Combination therapy with LY294002, a PI3K inhibitor, and sirolimus effectively inhibits leptin-enhanced neointimal hyperplasia. These data show that, in the setting of hyperleptinemia, higher doses of an mTOR inhibitor, or combination therapy with mTOR and PI3K inhibitors, inhibits neointimal hyperplasia after arterial injury. These studies may explain the higher rates of restenosis observed in diabetics treated with a sirolimus-eluting coronary stent and suggest a potential novel therapeutic approach for inhibiting in-stent restenosis in such patients.
Contact Endoscopy during Microlaryngeal Surgery: A New Technique for Endoscopic Examination of the Larynx (1995)

By means of a microcolpohysteroscope during microlaryngoscopy, the cells of superficial layers of the vocal cord epithelium, previously stained with methylene blue, were observed in vivo and in situ. Several parameters were evaluated: regularity of the epithelium, dimensions and color of the nucleus, nucleus-cytoplasm ratio, nucleus and cytoplasm contours, and presence of the nucleolus, mitosis, cytoplasmic inclusions, keratosis, and koilocytes, among others. The normal squamous epithelium of the vocal cord has a homogeneous cell arrangement, with a spheroid and isochromic nucleus, and a uniform nucleus-cytoplasm ratio. Specific cellular epithelial patterns in different disorders were observed, namely, chronic laryngitis, keratosis, dysplasia, papilloma, and malignant tumor. The present study on contact endoscopy during microlaryngeal surgery reports our first results with this original technique, performed in 68 patients.
Tn<i>5053</i> family transposons are <i>res</i> site hunters sensing plasmidal <i>res</i> sites occupied by cognate resolvases (1999)

DNA sequence database search revealed that most of Tn5053/Tn402 family transposons inserted into natural plasmids were located in putative res regions upstream of genes encoding various resolvase-like proteins. Some of these resolvase genes belonged to Tn3 family transposons and were closely related to the tnpR genes of Tn1721 and a recently detected Tn5044. Using recombinant plasmids containing fragments of Tn1721 or Tn5044 as targets in transposition experiments, we have demonstrated that Tn5053 displays striking insertional preference for the res regions of these transposons: more than 70% of Tn5053 insertion events occur in clusters inside the target res regions, while most remaining insertion events occur no further than 200 base pairs away from both sides of the res regions. We demonstrate that Tn5053 insertions (both into and outside a res region of the target plasmid) require the presence of a functional cognate resolvase gene either in cis or in trans. To our knowledge, this is the first case when a site-specific recombination system outside a transposon has been shown to be involved in transposition.
Mechanism of action of bisimidazoacridones, new drugs with potent, selective activity against colon cancer. (1995)

Antitumor bisimidazoacridones are bifunctional DNA binders which have recently been shown to selectively target human colon carcinoma cells in vitro and in vivo and appear to be excellent candidates for clinical development. We have studied the mechanism of action of one bisimidazoacridone, WMC26, which is 1,000-10,000 times more toxic to human colon carcinoma cells (HCT116) than to melanoma cells (SKMEL2) in vitro. Plasmid DNA exposed to WMC26 showed enhanced digestion by DNase I at A-T-rich sites, suggesting alterations in DNA conformation upon drug binding. These results led us to investigate whether WMC26 was selectively toxic due to a specific recognition of DNA bends by repair excinucleases, as has been demonstrated with the DNA bisintercalator, ditercalinium. Both prokaryotic and eukaryotic cells with intact repair capacity were shown to be selectively sensitive to WMC26, strongly indicating that excision repair plays a role in its toxicity. Confocal microscopy studies utilizing fluorescence of the WMC26 chromophore showed compound localization in the perinuclear cytoplasmic area, as had been previously noted for ditercalinium, indicating that cytoplasmic DNA could be the target. This irreversible accumulation of compound was gradually followed by vacuolization of the cytoplasm and cell death. Cell cycle analysis of both lines treated with WMC26 or with ditercalinium showed that, while the latter induced HCT116 growth arrest at G1-G0, WMC26 also blocked the cell cycle at G2-M; SKMEL2 cells did not undergo any changes in cell cycle as a result of either treatment. Our data show that WMC26 is 10-100 times more cytotoxic than ditercalinium in vitro. Like ditercalinium, WMC26 appears to exert its toxicity via cytoplasmic elements, through a mechanism involving excision repair processes. However, its highly selective cytotoxicity may stem from additional undefined targets in sensitive colon cancer cells.
Statistical bias in isotope ratios (2012)

This paper presents the mathematics of the systematic bias in the expected value of the ratio of two noise-corrected Poisson-distributed variables, such as ion counting measurements. Such bias can lead to the reporting of incorrect ratios and, in some cases, systematic correlations with other measurements which can impact the scientific interpretation. We describe a novel method of treating such measurements which results in a negligible, exponentially small bias. We also re-examine the conventional approach deriving an exact expression for the bias including the noise correction explicitly.
Loss of AtPDR8, a Plasma Membrane ABC Transporter of Arabidopsis thaliana, Causes Hypersensitive Cell Death Upon Pathogen Infection (2006)

Plants contain a large number of ATP-binding cassette (ABC) transporters belonging to different subclasses. AtPDR8 is the only member of the pleiotropic drug resistance (PDR) ABC transporter subclass in Arabidopsis that is constitutively highly expressed. In transgenic Arabidopsis plants harboring the AtPDR8 promoter fused to beta-glucuronidase (GUS), reporter expression was shown to be strong in the stomata and hydathode. In the stomata, transcripts of AtPDR8 were particularly frequent in the cells surrounding air spaces. Subcellular fractionation and immunochemical analysis showed that AtPDR8 was localized in the plasma membrane. When a knockout mutant of AtPDR8 (atpdr8) was infected with bacterial and oomycete pathogens, the plants exhibited chlorotic lesions and a hypersensitive response (HR)-like cell death. Cell death was detected in the atpdr8 mutants within 10 h of infection with the virulent bacterial pathogen, Pseudomonas syringae. As a result, the growth of P. syringae in the leaves of the atpdr8 mutant was reduced to 1% of that in the wild type. The defense response genes, PR-1, PR-2, PR-5, VPEgamma, AtrbohD and AtrbohF were highly expressed when the mutant plants were grown under non-sterile conditions. The expression of the AtPDR8 gene was enhanced by infection of virulent and avirulent bacterial pathogens. Our results indicate that AtPDR8 is a key factor controlling the extent of cell death in the defense response and suggest that AtPDR8 transports some substance(s) which is closely related to the response of plants to pathogens.
Multiple magnesium ions in the ribonuclease P reaction mechanism (1993)

The ribozyme ribonuclease (RNase) P cleaves precursor transcripts to produce the mature 5'-end of tRNAs. This hydrolysis reaction has a divalent cation requirement that is primarily catalytic, rather than structural; RNase P can be considered a metalloenzyme. Kinetic analysis shows that the RNase P catalytic mechanism has a cooperative dependence upon Mg2+ concentration. At least three Mg2+ ions are required for optimal activity, suggesting a multiple metal ion mechanism. The 2'-OH at the site of substrate cleavage may act as a ligand for a catalytically important Mg2+: deoxyribose substitution reduces the apparent number of Mg2+ bound from three to two and increases the apparent dissociation constant for Mg2+ from the micromolar to the millimolar range. In addition to these cation effects, the deoxyribose substitution reduces the rate of catalysis by 3400-fold; substitution with 2'-O-methyl at the cleavage site reduces the catalytic rate 10(6)-fold. If we presume no significant conformational effects of the substitutions, these results suggest that the 2'-OH serves as hydrogen-bond donor. The kinetic analysis of the catalytic mechanism is based upon the characterization of the pH dependence of the reaction. There is a hyperbolic (saturable) dependence on hydroxide concentration, with the half-maximal rate achieved at pH 8.0-8.5. The rate of the cleavage step is about 200 min-1 at pH 8.0, which is 500-fold faster than the steady-state parameter kcat.
Optical–optical double resonance laser spectroscopy of BaO (1975)

BaO molecules were sequentially excited by collinearly propagating radiation from two cw lasers, an argon ion laser (488.0 and 496.5-nm lines) and a tunable (560–630 nm) rhodamine 6G dye laser. This sequential excitation technique, called optical–optical double resonance (OODR), is a special case of two-photon spectroscopy in which two visible or uv wavelength photons of different frequencies resonantly excite a molecule from an initial level (v″,J″) to a final level (v*,J*) by way of a real intermediate level (v′,J′). Two types of optical double resonance experiments were performed on BaO. The first, excitation spectroscopy, revealed 19 vibronic levels of 1Σ+ electronic symmetry between 36 490 and 38 620 cm−1 above E (X 1Σ,re). These 19 1Σ+ levels belong to two or more perturbed electronic states. No 1Π levels were found, although levels belonging to the upper state of the BaO B (1Π) –X 1Σ Parkinson bands occur in this energy region. The second type of experiment, photoluminescence spectroscopy, enabled observation of extended rotationally resolved photoluminescence progressions out of various two-photon-excited levels (v*,J*) into BaO X 1Σ (v″=0–34). Vibrational energies and rotational constants obtained from these photoluminescence progressions were used to construct an RKR potential energy curve for BaO X 1Σ+ through v″=40, from which it was shown that the X 1Σ+ and a 3Π curves cross at r=0.276 nm and E=22 750 cm−1 [above E (X 1Σ,re)]. Laser frequency jitter of less than 10−3 cm−1 resulted in large intensity fluctuations of the OODR signal, implying that the double resonance linewidth was narrower than the Doppler width of the (v′,J′) → (v*,J*) transition. This sub-Doppler width effect resulted from excitation of (v′,J′) molecules that were velocity selected relative to the laser propagation direction.
Life Cycle of <i>Glomus Intraradix</i> in Root Organ Culture (1992)

The entire vegetative life cycle of the vesicular-arbuscular mycorrhizal fungus Glomus intraradix was followed in a simple monoxenic culture system using Ri T DNA-transformed carrot roots and non-transformed tomato roots as plant partners. Fungal development, from the growth of initial germ tubes to the formation of an external mycelium network and spore production, was observed nondestructively using light microscopy.Surface-sterilized spores isolated from pot culture constituted an excellent source of fungal inoculum. These spores germinated readily on the nutrient medium and only a low rate of contamination was recorded. Germ tubes approaching the surface of isolated roots changed their growth pattern and branched profusely in response to root factors. Throughout the growth process it was possible to observe directly the formation of terminal and intercalary secondary spores, numerous hyphal anastomoses and arbuscle-like structures, intracellular vesicles and spores. The extent of internal root colonization by G. intraradix was relatively limited, but it was sufficient to permit the in vitro formation of hundreds of new spores free of contaminants, which were viable and capable of colonizing host roots.
Elevation of Serum Albumin Levels in Nagase Analbuminemic Rats by Allogeneic Bone Marrow Cell Transplantation (2005)

We investigated the feasibility of correcting the congenital absence of albumin in Nagase analbuminemic rats (NARs) by allogeneic bone marrow cell transplantation (BMT). Seven-week-old male NARs were used as recipients, and 6- to 8-week-old male Sprague-Dawley (SD) rats were used as allograft donors. NARs were divided into three groups: a BMT group (n=10) in which bone marrow cells were infused into the liver; a hepatocyte transplantation (HCT) group (n=8) in which hepatocytes were transplanted into the liver, and a control group (n=8) in which PBS was injected into the portal vein. Serum albumin levels were measured as an indicator of the function of the grafted cells, and the phenotypic characteristics of the engrafted cells in the recipient's liver were assessed with immunohistochemical and immunofluorescence techniques. At 8 weeks after cell transplantation, the serum albumin levels of the BMT group and HCT group were significantly higher than in the control group. The hepatocyte-like cells derived from bone marrow cells expressed albumin in liver of the NARs. According to this result, bone marrow cells can differentiate into hepatocyte-like cells in vivo. The results show that BMT is an effective treatment for congenital analbuminemia in a rat model and suggest that allogeneic BMT can be used as an efficient therapy for hereditary metabolic diseases.
Deep convolutional neural networks for classifying head and neck cancer using hyperspectral imaging (2017)

Surgical cancer resection requires an accurate and timely diagnosis of the cancer margins in order to achieve successful patient remission. Hyperspectral imaging (HSI) has emerged as a useful, noncontact technique for acquiring spectral and optical properties of tissue. A convolutional neural network (CNN) classifier is developed to classify excised, squamous-cell carcinoma, thyroid cancer, and normal head and neck tissue samples using HSI. The CNN classification was validated by the manual annotation of a pathologist specialized in head and neck cancer. The preliminary results of 50 patients indicate the potential of HSI and deep learning for automatic tissue-labeling of surgical specimens of head and neck patients.
Efficient entity resolution methods for heterogeneous information spaces (2011)

The Web of Data encompasses a voluminous, yet constantly expanding collection of structured and semi-structured data sets. An important prerequisite for leveraging on them is the detection (and merge) of information that describe the same real-world entities, a task known as Entity Resolution. To enhance the efficiency of this quadratic task, blocking techniques are typically employed. They are, however, inapplicable to the Web of Data, due to the noise, the loose schema binding as well as the unprecedented heterogeneity inherent in it. In the context of my thesis, I focus on developing novel blocking methods that scale up Entity Resolution within such large, noisy, and heterogeneous information spaces. At their core lies an attribute-agnostic mechanism that relies exclusively on the values of entity profiles in order to build blocks effectively. The resulting set of blocks is processed efficiently by intelligent techniques that minimize the required number of comparisons. Any combination of block building and block processing methods is possible, allowing for high flexibility of the overall approach. Initial experimental studies on large, real-world data sets have produced quite promising results.
A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography (2014)

We present a power-efficient fiber-based imaging system capable of co-registered autofluorescence imaging and optical coherence tomography (AF/OCT). The system employs a custom fiber optic rotary joint (FORJ) with an embedded dichroic mirror to efficiently combine the OCT and AF pathways. This three-port wavelength multiplexing FORJ setup has a throughput of more than 83% for collected AF emission, significantly more efficient compared to previously reported fiber-based methods. A custom 900 µm diameter catheter ‒ consisting of a rotating lens assembly, double-clad fiber (DCF), and torque cable in a stationary plastic tube ‒ was fabricated to allow AF/OCT imaging of small airways in vivo. We demonstrate the performance of this system ex vivo in resected porcine airway specimens and in vivo in human on fingers, in the oral cavity, and in peripheral airways.
Spatiotemporal Changes of Eeg Activity During Waking-Sleeping Transition Period (1985)

To evaluate the spatiotemporal changes of EEG during waking-sleeping transition or hypnagogic period, spectral analysis of the five scalp EEG on the midline (Fpz, Fz, Cz, Pz and Oz) referenced to the left ear lobe was carried out on seven young male subjects. Power spectra from consecutive samples of 5.12 sec period with 0.2 Hz resolution were studied from 10 min before the manually scored stage 1 onset to 30 min after the onset of stage 1. The average power spectra over 1 min segments and corresponding coefficient of variation (CV) were determined for the frequency bands of delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), sigma (13-15 Hz) and beta (16-19 Hz). The latency score was defined as the time elapsed from the onset of stage 1 to the first epoch when the frequency band power, using the ANOVA significantly increased (or decreased) in comparison with the average level at the onset of stage 1. Median latency scores for each band were similar to the Cz scores, with a ranking, from early to late, of: alpha (2 min), theta (3 min), delta (5 min) and sigma (5 min). Significant change was not observed on the beta band activity. In terms of the EEG areas, the shortest latency was found in the theta band activity of the Fz EEG (2 min), and the longest was the sigma band activity of the Fpz and Oz EEG (8 min). The average stage 2 latency was 3.5 min when it was measured as time elapsed between the onset of stage 1 and 2. The average curves of delta, theta and alpha band CVs, started to increase just before or immediately after stage 1 onset and continued to increase for about 10 min. If the increased CV or unsteadiness of EEG activity is taken as a characteristic of the hypnagogic period, hypnagogic states may be considered to have continued until about 10 min after the stage 1 onset. Delta-theta activity showed a rapid rise in power after the onset of stage 1 for all areas. Delta power at the occipital, however, increased more gradually, and consistently remained at a lower level. The differences of delta power between Oz and other four electrode sites became clear at 7 min after the onset of stage 1. These regional differences may reflect the termination of hypnagogic effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes Due to a Progressive Defect in β-Cell Mass in Rats Transgenic for Human Islet Amyloid Polypeptide (HIP Rat) (2004)

The islet in type 2 diabetes is characterized by a deficit in beta-cell mass, increased beta-cell apoptosis, and impaired insulin secretion. Also, islets in type 2 diabetes often contain deposits of islet amyloid derived from islet amyloid polypeptide (IAPP), a 37-amino acid protein cosecreted with insulin by beta-cells. Several lines of evidence suggest that proteins with a capacity to develop amyloid fibrils may also form small toxic oligomers that can initiate apoptosis. The amino acid sequence of IAPP in rats and mice is identical and differs from that in humans by substitution of proline residues in the amyloidogenic sequence so that the protein no longer forms amyloid fibrils or is cytotoxic. In the present study, we report a novel rat model for type 2 diabetes: rats transgenic for human IAPP (the HIP rat). HIP rats develop diabetes between 5 and 10 months of age, characterized by an approximately 60% deficit in beta-cell mass that is due to an increased frequency of beta-cell apoptosis. HIP rats develop islet amyloid, but the extent of amyloid was not related to the frequency of beta-cell apoptosis (r = 0.10, P = 0.65), whereas the fasting blood glucose was (r = 0.77, P < 0.001). The frequency of beta-cell apoptosis was related to the frequency of beta-cell replication (r = 0.97, P < 0.001) in support of the hypothesis that replicating cells are more vulnerable to apoptosis than nondividing cells. The HIP rat provides additional evidence in support of the potential role of IAPP oligomer formation toward the increased frequency of apoptosis in type 2 diabetes, a process that appears to be compounded by glucose toxicity when hyperglycemia supervenes.
Identification of Tyrosine Residues in Vascular Endothelial Growth Factor Receptor-2/FLK-1 Involved in Activation of Phosphatidylinositol 3-Kinase and Cell Proliferation (2001)

Activation of vascular endothelial growth factor receptor-2 (VEGFR-2) plays a critical role in vasculogenesis and angiogenesis. However, the mechanism by which VEGFR-2 activation elicits these cellular events is not fully understood. We recently constructed a chimeric receptor containing the extracellular domain of human CSF-1R/c-fms, fused with the entire transmembrane and cytoplasmic domains of murine VEGFR-2 (Rahimi, N., Dayanir, V., and Lashkari, K. (2000) J. Biol. Chem. 275, 16986-16992). In this study we used VEGFR-2 chimera (herein named CKR) to elucidate the signal transduction relay of VEGFR-2 in porcine aortic endothelial (PAE) cells. Mutation of tyrosines 799 and 1173 individually on CKR resulted in partial loss of CKR's ability to stimulate cell growth. Double mutation of these sites caused total loss of CKR's ability to stimulate cell growth. Interestingly, mutation of these sites had no effect on the ability of CKR to stimulate cell migration. Further analysis revealed that tyrosines 799 and 1173 are docking sites for p85 of phosphatidylinositol 3-kinase (PI3K). Pretreatment of cells with wortmannin, an inhibitor of PI3K, and rapamycin, a potent inhibitor of S6 kinase, abrogated CKR-mediated cell growth. However, expression of a dominant negative form of ras (N(17)ras) and inhibition of the mitogen-activated protein kinase (MAPK) pathway by PD98059 did not attenuate CKR-stimulated cell growth. Altogether, these results demonstrate that activation of VEGFR-2 results in activation of PI3K and that activation of PI3K/S6kinase pathway, but not Ras/MAPK, is responsible for VEGFR-2-mediated cell growth.