gebhart/patrepeval huggingface dataset:
microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest (2015)

microRNA-449a (miR-449a) has been identified to function as a tumor suppressor in several types of cancers. However, the role of miR-449a in neuroblastoma has not been intensively investigated. We recently found that the overexpression of miR-449a significantly induces neuroblastoma cell differentiation, suggesting its potential tumor suppressor function in neuroblastoma. In this study, we further investigated the mechanisms underlying the tumor suppressive function of miR-449a in neuroblastoma. We observed that miR-449a inhibits neuroblastoma cell survival and growth through 2 mechanisms--inducing cell differentiation and cell cycle arrest. Our comprehensive investigations on the dissection of the target genes of miR-449a revealed that 3 novel targets- MFAP4, PKP4 and TSEN15 -play important roles in mediating its differentiation-inducing function. In addition, we further found that its function in inducing cell cycle arrest involves down-regulating its direct targets CDK6 and LEF1. To determine the clinical significance of the miR-449a-mediated tumor suppressive mechanism, we examined the correlation between the expression of these 5 target genes in neuroblastoma tumor specimens and the survival of neuroblastoma patients. Remarkably, we noted that high tumor expression levels of all the 3 miR-449a target genes involved in regulating cell differentiation, but not the target genes involved in regulating cell cycle, are significantly correlated with poor survival of neuroblastoma patients. These results suggest the critical role of the differentiation-inducing function of miR-449a in determining neuroblastoma progression. Overall, our study provides the first comprehensive characterization of the tumor-suppressive function of miR-449a in neuroblastoma, and reveals the potential clinical significance of the miR-449a-mediated tumor suppressive pathway in neuroblastoma prognosis.
Air-filled proteinaceous microbubbles: synthesis of an echo-contrast agent. (1991)

Air-filled microbubbles are in clinical use as echo-contrast agents for sonographic applications. The synthesis of aqueous suspensions of air-filled proteinaceous microbubbles involves the ultrasonic irradiation of aqueous protein solutions in the presence of O2. Yields and size distributions of human and bovine serum albumin microbubbles have been determined as a function of various experimental parameters. The chemical nature of these microbubbles and the origin of their remarkably long lifetimes have been explored. The microbubbles are held together primarily by interprotein cross-linking of cysteine residues. The principal cross-linking agent is superoxide created by the extremely high temperatures produced during acoustic cavitation.
Formation, conversion, and utilization of isorhodopsin, rhodopsin, and porphyropsin by rod photoreceptors in the Xenopus retina. (1978)

The visual pigment content of rod photoreceptors in Xenopus larvae was reduced greater than 90% through a combination of vitamin A-deficient diet and constant light. Thereafter, a dose of either all-trans-retinol or 9-cis-retinal was injected intramuscularly, leading to the formation of a rhodopsin (lambdamax 504 nm) or isorhodopsin (lambdamax 487-493 nm) pigment, respectively. Electrophysiological measurements were made of the threshold and spectral sensitivity of the aspartate-isolated PIII (photoreceptoral) component of the electroretinogram. These measures established that either rhodopsin or isorhodopsin subserved visual transduction with the same efficiency as the 519 nm porphyropsin pigment encountered normally. When animals with rhodopsin or isorhodopsin were kept in darkness or placed on a cyclical lighting regimen for 8 days, retinal densitometry showed that either pigment was being converted to porphyropsin; significantly more porphyropsin was formed as a result of cyclical lighting than after complete darkness.
Walking Patterns of Normal Men (1964)

A simple and inexpensive photographic method has been developed whereby many kinematic components of the walking act in the sagittal, frontal, and transverse planes can be measured and related temporally. A factorial design was used to study the displacement patterns of sixty normal men who ranged in age from twenty to sixty-five years and in height from sixty-one to seventy-four inches. Each subject's weight was within normal limits for his height and frame size. There was striking similarity in the duration of successive phases of stance, swing, and double-limb support during the same walking trial and during repeated trials of the same subject. Step and stride length and stride width showed the same striking similarity. Foot angles, however, showed greater individual variability. The differences in timing and stride dimensions did not relate systematically with age. However, the subjects sixty to sixty-five years old differed from younger subjects in that they took shorter steps and strides and showed a greater degree of out-toeing. The only variables which related systematically with height were the step and stride lengths, with the tall subjects taking the longest steps and strides and the short subjects, the shortest. Seven displacement patterns of free-cadence walking were analyzed for sixty normal men from twenty to sixty-five years old and from sixty-one to seventy-four inches tall. These displacement patterns include sagittal rotation of the pelvis, hip, knee, and ankle and vertical, lateral, and forward movement of the trunk. Each movement pattern was strikingly similar for repeated trials of the same subject and for subjects in the various age and height groups. Slight differences in the magnitude of hip flexion excursion occurred, which showed a low positive correlation with age and a similarly low but negative correlation with height. There was no evidence of presenile changes in these excursions among our oldest subjects, except for some decrease in the magnitude of ankle extension at the end of the stance phase. The serial transverse rotations of the pelvis and thorax have been analyzed in free-cadence walking of sixty normal men. Although there was striking similarity in these excursions for repeated trials of the same subject, there was wide variation in these excursions among the subjects in similar age and height categories. These variations suggest that pelvic and thoracic rotation are not obligatory elements of normal gait. The decreased pelvic rotation in the group sixty to sixty-five years old may possibly represent another aspect of the presenile pattern of walking.
Preparation of aromatic geraniol analogues via a Cu(I)-mediated Grignard coupling (2003)

Difunctional allylic terpenes are important synthetic building blocks. Functionalization of protected geranyl derivatives by SeO2/t-BuO2H adsorbed on SiO2 provides a convenient route to such compounds. The chosen protecting groups clearly influence the oxidation process. Also, an efficient synthesis of 2-geranylphenol derivatives via a Cu(I)-mediated Grignard coupling of 2-lithiophenols and geranyl substrates was developed.
C-C CHEMOKINES IN THE VITREOUS OF PATIENTS WITH PROLIFERATIVE VITREORETINOPATHY AND PROLIFERATIVE DIABETIC RETINOPATHY (1998)

Monocyte chemotactic protein-1 might be involved in the recruitment of macrophages and monocytes into the vitreous of eyes with proliferative vitreoretinal disorders.
Blockade of the Inward Rectifying Potassium Current Terminates Ventricular Fibrillation in the Guinea Pig Heart (2003)

The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics.
The Relation between Shift Work, Sleepiness, Fatigue and Accidents in Iranian Industrial Mining Group Workers (2009)

The aim of this study was to examine the rate of fatigue and sleepiness around the shift and non-shift workers and its relation to occupational accidents. This was a cross-sectional study on the workers of Iranian Industrial Mining Group. They included 137 shift workers as the case and 130 non-shift workers as the control. A multi-part questionnaire including demographic characteristics, Piper Fatigue Scale and Epworth Sleepiness Scale were applied. The chi(2) test and t-test were used to measure differences between variables. The mean of PFS scores in the two groups was significantly different (p=0.045), but the difference in the mean of ESS scores was not significant. Shift workers with the reported accident had a higher score on fatigue than shift workers with no accident (p<0.001) whereas the difference in the number of accidents in the two groups was not related significantly to the rate of sleepiness. The rate of fatigue and the number of the work accidents was more in the shift workers. Also, fatigue had a stronger relationship with the occupational accidents as compared to sleepiness. It seems that evaluation of fatigue as compared to sleepiness is a more accurate factor for preventing work accidents.
p130CAS Forms a Signaling Complex with the Adapter Protein CRKL in Hematopoietic Cells Transformed by the BCR/ABL Oncogene (1996)

The Philadelphia chromosome (Ph) translocation generates a chimeric tyrosine kinase oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML) and a type of acute lymphoblastic leukemia (ALL). In primary samples from virtually all patients with CML or Ph+ALL, the CRKL adapter protein is tyrosine phosphorylated and physically associated with p210(BCR/ABL). CRKL has one SH2 domain and two SH3 domains and is structurally related to c-CRK-II (CRK) and the v-Crk oncoprotein. We have previously shown that CRKL, but not the related adapter protein c-CRK, is tyrosine phosphorylated in cell lines transformed by BCR/ABL, and that CRKL binds to BCR/ABL through the CRKL-SH3 domains. Furthermore, the CRKL-SH2 domain has been shown to bind one or more cellular proteins, one of which is p120(CBL). Here we demonstrate that another cellular protein linked to BCR/ABL through the CRKL-SH2 domain is p130(CAS). p130(CAS) was found to be tyrosine phosphorylated and associated with CRKL in BCR/ABL expressing cell lines and in samples obtained from CML and ALL patients, but not in samples from controls. In both normal and BCR/ABL transformed cells, p130(CAS) was detected in focal adhesion-like structures, as was BCR/ABL. In normal cells, the focal adhesion proteins tensin, p125(FAK), and paxillin constitutively associated with p130(CAS). However, in BCR/ABL transformed cells, the interaction between p130(CAS) and tensin was disrupted, while the associations between p130(CAS), p125(FAK), and paxillin were unaffected. These results suggest that the BCR/ABL oncogene could alter the function of p130(CAS) in at least three ways: tyrosine phosphorylation, inducing constitutive binding of CRKL to a domain in p130(CAS) containing Tyr-X-X-Pro motifs (substrate domain), and disrupting the normal interaction of p130(CAS) with the focal adhesion protein tensin. These alterations in the structure of signaling proteins in focal adhesion like structures could contribute to the known adhesion abnormalities in CML cells.
Sequence requirements for oligodeoxyribonucleotide inhibitory activity (2005)

Inhibitory oligonucleotides (IN-ODN) differing from stimulatory CpG ODN (ST-ODN) by as few as two bases can block ST-ODN-induced proliferation, apoptosis protection and IL-6 secretion in B lymphocytes and the production of IL-12p40 by non-B cells. The main objective of this study was to determine the ODN sequence requirements for inhibition in mice. Starting with a strongly inhibitory 15-mer prototype phosphorothioate sequence, we tested the 60 sequences that differed from the prototype by one base, revealing the three areas that are critical for activity. Between these areas were the spacer sequences where base composition mattered little, but the number of bases was important. Truncation of three bases at the 3' end of the 15-mer and one at the 5' end was tolerated with minimal loss of activity. This approach yielded an 'optimal' sequence of 5' CC x notC notC xxGGGx or CC x notC notC xGGGxx 3', where x is any base. The sequence requirements for optimal inhibition of B cell responses to Type B (K) ODN and mixed splenocyte IL-12p40 responses to Type A (D) ODN were strikingly similar. Inhibition of ST-ODN by IN-ODN was competitive. A hypothetical model of the ODN-binding site is proposed. Synthetic IN-ODN with the sequence characteristics defined here should provide antidotes for excessive innate reactions to DNA.
Mucosally induced Immunological Tolerance, Regulatory T Cells and the Adjuvant Effect by Cholera Toxin B Subunit (2009)

Induction of peripheral immunological tolerance by mucosal administration of selected antigens (Ags) ('oral tolerance') is an attractive, yet medically little developed, approach to prevent or treat selected autoimmune or allergic disorders. A highly effective way to maximize oral tolerance induction for immunotherapeutic purposes is to administer the relevant Ag together with, and preferably linked to the non-toxic B subunit protein of cholera toxin (CTB). Oral, nasal or sublingual administration of such Ag/CTB conjugates or gene fusion proteins have been found to induce tolerance with superior efficiency compared with administration of Ag alone, including the suppression of various autoimmune disorders and allergies in animal models. In a proof-of-concept clinical trial in patients with Behcet's disease, this was extended with highly promising results to prevent relapse of autoimmune uveitis. Tolerization by mucosal Ag/CTB administration results in a strong increase in Ag-specific regulatory CD4(+) T cells, apparently via two separate pathways: one using B cells as APCs and leading to a strong expansion of Foxp3(+) Treg cells which can both suppress and mediate apoptotic depletion of effector T cells, and one being B cell-independent and associated with development of Foxp3(-) regulatory T cells that express membrane latency-associated peptide and transforming growth factor (TGF-beta) and/or IL-10. The ability of CTB to dramatically increase mucosal Ag uptake and presentation by different APCs through binding to GM1 ganglioside (which makes most B cells effective APCs irrespective of their Ag specificity), together with CTB-mediated stimulation of TGF-beta and IL-10 production and inhibition of IL-6 formation may explain the dramatic potentiation of oral tolerance by mucosal Ags presented with CTB.
Avidin attachment to biotinylated amino groups of the erythrocyte membrane eliminates homologous restriction of both classical and alternative pathways of the complement (1993)

Lysis of avidin-coated biotinylated sheep red blood cells (RBC) via the classical pathway of homologous (sheep) and heterologous (guinea pig) complement has been studied. The minimal surface density of avidin inducing antibody-dependent lysis via the classical pathway is smaller than that inducing antibody-independent lysis via the alternative pathway. Heterologous lysis via the classical pathway does not depend on the mode of avidin attachment: both biotinylation of membrane amino groups and insertion of biotinyl-lipid into the membrane provide the same lysis of avidin-coated RBCs by guinea pig serum in the presence of anti-avidin antibody. Avidin-free sheep RBC sensitized with hemolytic anti-RBC antibody were lysed by guinea pig, but not by sheep serum, confirming high efficiency of homologous restriction of the complement. However, avidin-coated RBCs were lysed by homologous serum in the presence of anti-avidin antibody at low surface density of avidin attached. The elimination of the homologous restriction depends on the mode of avidin attachment: biotinylation of membrane amino groups provides antibody-mediated lysis via the classical pathway of homologous complement, while insertion of biotinyl-lipid does not provide lysis.
Isolated Bronchi from Asthmatics Are Hyperresponsive to Adenosine, which Apparently Acts Indirectly by Liberation of Leukotrienes and Histamine (1992)

Bronchial hyperresponsiveness can be demonstrated in asthmatic subjects by inhalation of adenosine, but the action of adenosine at the level of the human airway smooth muscle has received comparatively little attention. We have previously observed that bronchi isolated from one asthmatic patient contracted in response to adenosine. We have therefore, during the course of a 3-yr study, further characterized the effects of adenosine in bronchi prepared from surgical specimens of lung tissue of asthmatics and of nonasthmatics. Contraction responses were always studied in vitro the same day the tissues were obtained. Bronchi from asthmatics (19 strips from six patients) were more sensitive to adenosine than were bronchi from nonasthmatics (21 strips, seven patients). In contrast, there was no difference in sensitivity to histamine or leukotriene C4 between the two groups, nor was the maximal tissue contractility different. The contractile effect of adenosine was inhibited by the adenosine A1-antagonist 2-thio-[(1,3-dipropyl)-8-cyclopentyl]-xanthine as well as by the dual A1 and A2 antagonists 8-(p-sulfo)-phenyltheophylline and theophylline. The combination of leukotriene antagonism (receptor-antagonist ICI 198,615 or biosynthesis inhibitor MK-886) and histamine antagonism (antihistamines mepyramine and metiamide) blocked the contractile effects of adenosine, suggesting that adenosine acts indirectly by liberation of leukotrienes and histamine, possibly from mast cells. The findings of increased sensitivity to adenosine in bronchi from asthmatics to our knowledge represents the first evidence of increased bronchial reactivity in vitro in asthmatics.
Energy variance criterion and threshold tuning scheme for high impedance fault detection (1999)

This paper presents a new approach to the detection of high impedance fault (HIF). The proposed approach (or detector which implements this approach) has four distinct features. First, the detector input signal is the three-phase unbalanced current (or feeder 3I/sub 0/), rather than the conventional three individual phase-currents. Secondly, the detector is designed by monitoring the energy variance for the second, fourth and sixth harmonics of 3I/sub 0/ individually, and by requiring the increment of randomness of all these harmonics to indicate an HIF. Thirdly, a self-tuning scheme based on the statistical confidence is applied to the automatic setting of threshold level for the energy variances monitored. Fourthly, effective counters are designed to detect both persistent and intermittent arcings. The detector has been tested on 51 stages faults and 8 unfaulted feeders. The test results show that the detector can have 100% faults detection rate so long as the arcing current at fault location is not less then 5 A. As to the dependability tests, no false alarm (or tripping) has happened for all of the unfaulted feeders under test. These feeders either supply special (including arc furnace) load, or have leakage current (referring to the intermittent zero-sequence load due to the feeder location along coast), or are under the normal capacitor or load switchings, and dependability and for the limitation of proposed fault detection method are presented.
A Rev-Independent Human Immunodeficiency Virus Type 1 (HIV-1)-Based Vector That Exploits a Codon-Optimized HIV-1 gag-pol Gene (2000)

The human immunodeficiency virus (HIV) genome is AU rich, and this imparts a codon bias that is quite different from the one used by human genes. The codon usage is particularly marked for the gag, pol, and env genes. Interestingly, the expression of these genes is dependent on the presence of the Rev/Rev-responsive element (RRE) regulatory system, even in contexts other than the HIV genome. The Rev dependency has been explained in part by the presence of RNA instability sequences residing in these coding regions. The requirement for Rev also places a limitation on the development of HIV-based vectors, because of the requirement to provide an accessory factor. We have now synthesized a complete codon-optimized HIV-1 gag-pol gene. We show that expression levels are high and that expression is Rev independent. This effect is due to an increase in the amount of gag-pol mRNA. Provision of the RRE in cis did not lower protein or RNA levels or stimulate a Rev response. Furthermore we have used this synthetic gag-pol gene to produce HIV vectors that now lack all of the accessory proteins. These vectors should now be safer than murine leukemia virus-based vectors.
Highly Efficient Dye-Sensitized Solar Cells Based on Carbon Black Counter Electrodes (2006)

Carbon black was employed as the catalyst for triiodide reduction on fluorine-doped tin oxide glass substrates (FTO-glass) used as counter electrodes in platinum-free dye-sensitized solar cells. The fill factors were strongly dependent on the thickness of the carbon layer, and the light energy conversion efficiency also increased up to a thickness of . The charge-transfer resistance of the carbon counter electrode decreased with the thickness of the carbon layer. The for the thicker carbon layer is less than three times that for the platinized FTO-glass. The highest cell efficiency was 9.1% under light intensity (1 sun AM 1.5 light, , , fill ).
Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients (2003)

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception. The aim of the study was to determine if local anesthetic blockade of peripheral visceral nociceptive input reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. Ten women with IBS (mean age 30+/-10 years) and ten control subjects (all women) (mean age 29+/-7 years) rated pain intensity and unpleasantness to distension of the rectum (35 mmHg) and thermal stimulation (47 degrees C) of the foot before and after rectal administration of either lidocaine jelly or saline jelly in a double blind crossover design. Intrarectal lidocaine (300 mg) reduced reported rectal and cutaneous pain in all of the IBS patients. The effects were statistically much greater than those of placebo and most of the effects were present within 5-15 min after the onset of the treatment. In the control subjects, rectal lidocaine did not decrease pain report from visceral and cutaneous stimuli. The results of this study support the hypothesis that local anesthetic blockade of peripheral impulse input from the rectum/colon reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. The results provide further evidence that visceral hyperalgesia and secondary cutaneous hyperalgesia in IBS reflects central sensitization mechanisms that are dynamically maintained by tonic impulse input from the rectum/colon. Rectal administration of lidocaine jelly may also be a safe and effective means of reducing pain symptoms in IBS patients.