gebhart/patrepeval huggingface dataset:
N6‐methyladenosine modification in mRNA: machinery, function and implications for health and diseases (2015)

N6-methyladenosine (m(6) A) modification in mRNA is extremely widespread, and functionally modulates the eukaryotic transcriptome to influence mRNA splicing, export, localization, translation, and stability. Methylated adenines are present in a large subset of mRNAs and long noncoding RNAs (lncRNAs). Methylation is reversible, and this is accomplished by the orchestrated action of highly conserved methyltransferase (m(6) A writer) and demethylase (m(6) A eraser) enzymes to shape the cellular 'epitranscriptome'. The engraved 'methyl code' is subsequently decoded and executed by a group of m(6) A reader/effector components, which, in turn, govern the fate of the modified transcripts, thereby dictating their potential for translation. Reversible mRNA methylation thus adds another layer of regulation at the post-transcriptional level in the gene expression programme of eukaryotes that finely sculpts a highly dynamic proteome in order to respond to diverse cues during cellular differentiation, immune tolerance, and neuronal signalling.
Automated Solid-Phase Extraction and Measurement of Perfluorinated Organic Acids and Amides in Human Serum and Milk (2004)

Organic fluorochemicals are used in multiple commercial applications including surfactants, lubricants, paints, polishes, food packaging, and fire-retarding foams. Recent scientific findings suggest that several perfluorochemicals (PFCs), a group of organic fluorochemicals, are ubiquitous contaminants in humans and animals world wide. Furthermore, concern has increased about the toxicity of these compounds. Therefore, monitoring human exposure to PFCs is important. We have developed a high-throughput method for measuring trace levels of 13 PFCs (2 perfluorosulfonates, 8 perfluorocarboxylates, and 3 perfluorosulfonamides) in serum and milk using an automated solid-phase extraction (SPE) cleanup followed by high-performance liquid chromatography-tandem mass spectrometry. The method is sensitive, with limits of detection between 0.1 and 1 ng in 1 mL of serum or milk, is not labor intensive, involves minimal manual sample preparation, and uses a commercially available automated SPE system. Our method is suitable for large epidemiologic studies to assess exposure to PFCs. We measured the serum levels of these 13 PFCs in 20 adults nonoccupationally exposed to these compounds. Nine of the PFCs were detected in at least 75% of the subjects. Perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), 2-(N-methylperfluorooctane-sulfonamido)acetate (Me-PFOSA-AcOH), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA) were found in all of the samples. The concentration order and measured levels of PFOS, PFOA, Me-PFOSA-AcOH, and PFHxS compared well with human serum levels previously reported. Although no human data are available for the perfluorocarboxylates (except PFOA), the high frequency of detection of PFNA and other carboxylates in our study suggests that human exposure to long-alkyl-chain perfluorocarboxylates may be widespread. We also found PFOS in the serum and milk of rats administered PFOS by gavage, but not in the milk of rats not dosed with PFOS. Furthermore, we did not detect most PFCs in two human milk samples. These findings suggest that PFCs may not be as prevalent in human milk as they are in serum. Additional studies are needed to determine whether environmental exposure to PFCs can result in PFCs partitioning into milk. Large epidemiological studies to determine the levels of PFCs among the U.S. general population are warranted.
Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland (1998)

In vitro studies have been performed to demonstrate and characterize specific binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary gland and different human brain regions. A binding assay for sGHS was established using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high specific activity at the Tyr residue. Specific binding sites for 125I-labelled Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland and hypothalamus, but they were also present in other brain areas such as choroid plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related differences. In contrast, negligible binding was found in the thalamus, striatum, substantia nigra, cerebellum and corpus callosum. The binding of 125I-labelled Tyr-Ala-hexarelin to membrane-binding sites is a saturable and reversible process, depending on incubation time and pH of the buffer. Scatchard analysis of the binding revealed a finite number of binding sites in the hypothalamus and pituitary gland with a dissociation constant (Kd) of (1.5 +/- 0.3) x 10(-9) and (2.1 +/- 0.4) x 10(-9) mol/l respectively. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipids are essential for the binding of 125I-labelled Tyr-Ala-hexarelin. The binding of 125I-labelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was displaced in a dose-dependent manner by different unlabelled synthetic peptidyl (Tyr-Ala-hexarelin, GHRP2, hexarelin, GHRP6) and non-peptidyl (MK 0677) sGHS. An inhibition of the specific binding was also observed when binding was performed in the presence of [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P, a substance P antagonist that has been found to inhibit GH release in response to sGHS. In contrast, no competition was observed in the presence of other neuropeptides (GHRH, somatostatin, galanin or Met-enkephalin) which have a known influence on GH release. In conclusion, the present data demonstrate that sGHS have specific receptors in human brain and pituitary gland and reinforce the hypothesis that these compounds could be the synthetic counterpart of an endogenous GH secretagogue involved in the neuroendocrine control of GH secretion and possibly in other central activities.
Conjugates of Superoxide Dismutase with the Fc Fragment of Immunoglobulin G (1991)

We constructed conjugates of superoxide dismutase (SOD) and the Fc fragment of human immunoglobulin G. The lysyl residues of bovine erythrocyte Cu,Zn-SOD were covalently linked with cysteine residues of the Fc fragment using N-succinimidyl 4-(N-maleimido)-butylate as a crosslinking agent. Analysis by gel filtration and SDS-PAGE revealed that the conjugates were composed of one molecule of SOD linked with one molecule of Fc [SOD-(Fc)1] and one SOD molecule linked with several Fc molecule [SOD-(Fc)n]. The resulting SOD-Fc conjugates retained more than 90% of the enzyme activity of SOD. When those conjugates were administered intravenously to mice, the half-lives of SOD activity in the circulation were 29 and 42 h for SOD-(Fc)1 and SOD-(Fc)n, respectively, while free SOD had a half-life of 5 min. Intravenous administration of the conjugates to mice markedly repressed the increase in serum glutamic-oxaloacetic transaminase (GOT) activity induced by paraquat. These results suggest that SOD-Fc conjugates, which have long half-lives, effectively perform dismutation of superoxide radicals and may be useful for preventing tissue injury caused by hazardous oxygen metabolites.
The Gut-enriched Krüppel-like Factor (Krüppel-like Factor 4) Mediates the Transactivating Effect of p53 on the p21 Promoter (2000)

An important mechanism by which the tumor suppressor p53 maintains genomic stability is to induce cell cycle arrest through activation of the cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene. We show that the gene encoding the gut-enriched Krüppel-like factor (GKLF, KLF4) is concurrently induced with p21(WAF1/Cip1) during serum deprivation and DNA damage elicited by methyl methanesulfonate. The increases in expression of both Gklf and p21(WAF1/Cip1) due to DNA damage are dependent on p53. Moreover, during the first 30 min of methyl methanesulfonate treatment, the rise in Gklf mRNA level precedes that in p21(WAF1/Cip1), suggesting that GKLF may be involved in the induction of p21(WAF1/Cip1). Indeed, GKLF activates p21(WAF1/Cip1) through a specific Sp1-like cis-element in the p21(WAF1/Cip1) proximal promoter. The same element is also required by p53 to activate the p21(WAF1/Cip1) promoter, although p53 does not bind to it. Potential mechanisms by which p53 activates the p21(WAF1/Cip1) promoter include a physical interaction between p53 and GKLF and the transcriptional induction of Gklf by p53. Consequently, the two transactivators cause a synergistic induction of the p21(WAF1/Cip1) promoter activity. The physiological relevance of GKLF in mediating p53-dependent induction of p21(WAF1/Cip1) is demonstrated by the ability of antisense Gklf oligonucleotides to block the production of p21(WAF1/Cip1) in response to p53 activation. These findings suggest that GKLF is an essential mediator of p53 in the transcriptional induction of p21(WAF1/Cip1) and may be part of a novel pathway by which cellular responses to stress are modulated.
Microfabricated electrospray emitter arrays with integrated extractor and accelerator electrodes for the propulsion of small spacecraft (2014)

Microfabricated electrospray thrusters could revolutionize the spacecraft industry by providing efficient propulsion capabilities to micro and nano satellites (1â100 kg). We present the modeling, design, fabrication and characterization of a new generation of devices, for the first time integrating in the fabrication process individual accelerator electrodes capable of focusing and accelerating the emitted sprays. Integrating these electrodes is a key milestone in the development of this technology; in addition to increasing the critical performance metrics of thrust, specific impulse and propulsive efficiency, the accelerators enable a number of new system features such as power tuning and thrust vectoring and balancing. Through microfabrication, we produced high density arrays (213 emitters cmâ2) of capillary emitters, assembling them at wafer-level with an extractor/accelerator electrode pair separated by micro-sandblasted glass. Through IV measurements, we could confirm that acceleration could be decoupled from the extraction of the sprayâan important element towards the flexibility of this technology. We present the largest reported internally fed microfabricated arrays operation, with 127 emitters spraying in parallel, for a total beam of 10â30 Î¼A composed by 95% of ions. Effective beam focusing was also demonstrated, with plume half-angles being reduced from approximately 30Â° to 15Â° with 2000 V acceleration. Based on these results, we predict, with 3000 V acceleration, thrust per emitter of 38.4 nN, specific impulse of 1103 s and a propulsive efficiency of 22% with &lt;1 mW/emitter power consumption.
Extrasynaptic NMDA Receptors Couple Preferentially to Excitotoxicity via Calpain-Mediated Cleavage of STEP (2009)

NMDA receptor (NMDAR)-mediated excitotoxicity plays an important role in several CNS disorders, including epilepsy, stroke, and ischemia. Here we demonstrate the involvement of striatal-enriched protein tyrosine phosphatase (STEP) in this critical process. STEP(61) is an alternatively spliced member of the family that is present in postsynaptic terminals. In an apparent paradox, STEP(61) regulates extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, two proteins with opposing functions; activated p38 promotes cell death, whereas activated ERK1/2 promotes cell survival. We found that synaptic stimulation of NMDARs promoted STEP(61) ubiquitination and degradation, concomitant with ERK1/2 activation. In contrast, extrasynaptic stimulation of NMDARs invoked calpain-mediated proteolysis of STEP(61), producing the truncated cleavage product STEP(33) and activation of p38. The calpain cleavage site on STEP was mapped to the kinase interacting motif, a domain required for substrate binding. As a result, STEP(33) neither interacts with nor dephosphorylates STEP substrates. A synthetic peptide spanning the calpain cleavage site efficiently reduced STEP(61) degradation and attenuated p38 activation and cell death in slice models. Furthermore, this peptide was neuroprotective when neurons were subjected to excitotoxicity or cortical slices were exposed to ischemic conditions. These findings suggest a novel mechanism by which differential NMDAR stimulation regulates STEP(61) to promote either ERK1/2 or p38 activation and identifies calpain cleavage of STEP(61) as a valid target for the development of neuroprotective therapy.
Evolve or Die (2016)

Maintaining the highest levels of availability for content providers is challenging in the face of scale, network evolution and complexity. Little, however, is known about failures large content providers are susceptible to, and what mechanisms they employ to ensure high availability. From a detailed analysis of over 100 high-impact failure events in a global-scale content provider encompassing several data centers and two WANs, we quantify several dimensions of availability failures. We find that failures are evenly distributed across different network types and planes, but that a large number of failures happen when a management operation is in progress within the network. We discuss some of these failures in detail, and also describe our design principles for high availability motivated by these failures, including using defense in depth, maintaining consistency across planes, failing open on large failures, carefully preventing and avoiding failures, and assessing root cause quickly. Our findings suggest that, as networks become more complicated, failures lurk everywhere, and, counter-intuitively, continuous incremental evolution of the network can, when applied together with our design principles, result in a more robust network.
Study of spectral sensing using electro-optic films (2009)

Fundamental studies on light interacting with liquid crystals (LCs) and polymers have led to innovative application like the omnipresent LCDs, revolutionizing the display industry. This thesis focuses on manipulation of optical propagation through LC/polymer two phase composite material set and in-depth understanding of these systems by studying their morphology and microscopic interactions for multiwavelength sensing applications.Holographically formed Polymer Dispersed Liquid Crystals (HPDLCs) are the composite photorefractive material used in this work. They consist of LC nanodroplets confined in a polymer matrix, arranged in periodic planes. Applying an electric field across them modifies their periodic refractive index to a uniform refractive index state, due to LC realignment. This transforms the reective HPDLCs into an optically transparent state.Fabricating and assembling HPDLCs in different configurations enables wavelength filtering by controlling their optical lineshape output, for wavelength sensing applications. To increase the range of wavelengths spanned, these electro-optic thin films are arranged in serial and parallel design. A novel dynamic time multiplexing technique is used to improve the spectral range of individual HPDLC unit.These types of field controllable HPDLC wavelength filtering devices have remote sensing, imaging spectrometry applications like hyperspectral and multispectral imaging to detect specific spectral signature of an unknown remote object source. Comparing the detected spectra to a database of known spectral fingerprints enables identification of the unknown entity.To further fundamentally comprehend the LC polymer interaction in HPDLC systems structural analysis data using microscopy and spectroscopy techniques is presented. To interpret the nano-scale structure accurately and better understand the confined LC behavior, variable pressure scanning electron microscopy and electron spin resonance spectroscopy is used here for the first time. Berreman 4 4 matrix technique and a phenomenological diffusion model are presented to model and predict their optical output behavior and their multipart wavelength lineshapes. In summary this dissertation focuses on study of multi spectral sensing using HPDLCs, their fundamental studies along with modeling their behavior.%%%%Ph.D., Electrical Engineering  – Drexel University, 2009
Metalorganic vapor-phase epitaxial growth and characterization of vertical InP nanowires (2003)

Highly dense and free-standing InP nanowire structures of vertical orientation were grown by the metalorganic vapor-phase epitaxial technique using colloidal Au nanoparticles as the catalyst. Scanning electron microscopy and transmission electron microscopy showed that the nanowires were single crystalline with 〈111〉 growth direction and of uniform length of about 700 nm, and most of them had diameter in the range of 20–25 nm. Photoluminescence measurements, carried out at room temperature as well as at 77 K, showed a significant blueshift in the peak position compared to bulk InP due to the quantum confinement of the carriers in the nanowires. The successful growth of these nanowires opens up the possibility of realizing various nanoscale devices on the wafer scale in the bottom-up approach.
Characterization of T1 bias in skeletal muscle from fat in MOLLI and SASHA pulse sequences: Quantitative fat‐fraction imaging with T1 mapping (2016)

Fat results in negative or positive shifts in native tissue T<sub>1</sub> measured with MOLLI and SASHA over a narrow range of off-resonance frequencies; T<sub>1</sub> shifts from fat can be used to accurately quantify FF. Magn Reson Med 77:237-249, 2017. © 2016 Wiley Periodicals, Inc.
Quantification of Vuggy Porosity in a Dolomite Reservoir from Borehole Images and Core, Dagger Draw Field, New Mexico (1998)

Abstract Vugs, which are large irregular pores, are a key pore type in many carbonate reservoirs. Because of coarse sample rate and limited vertical resolution, conventional wireline logs commonly mask vuggy porosity. This becomes a major problem when logging tools combine high vuggy porosity with low matrix porosity to derive average porosity values that fall below arbitrary commercial cutoffs. Non-completion of such zones commonly results in bypassed pay. Borehole-imaging logs are high-resolution, oriented electronic "pictures" of the wellbore made by electrical or acoustic devices. Pixel-counting techniques, when applied to borehole images, can be used to detect and quantify vugs. The purpose of this study is to calibrate vugs quantified from borehole images to those quantified from digitally scanned core. Samples studied are vuggy dolomites of the Cisco and Canyon Formations (Pennsylvanian), Dagger Draw field, Eddy County, New Mexico. Results suggest that the neutron log is a good total-porosity device. However, this log suppresses the evidence for vuggy porosity which can lead to bypassed pay.
Use of Skeletal Muscle Tissue in Peripheral Nerve Repair: Review of the Literature (2004)

The management of peripheral nerve injury continues to be a major clinical challenge. The most widely used technique for bridging defects in peripheral nerves is the use of autologous nerve grafts. This technique, however, necessitates a donor nerve and corresponding deficit. Many alternative techniques have thus been developed. The use of skeletal muscle tissue as graft material for nerve repair is one example. The rationale regarding the use of the skeletal muscle tissue technique is the availability of a longitudinally oriented basal lamina and extracellular matrix components that direct and enhance regenerating nerve fibers. These factors provide superiority over other bridging methods as vein grafts or (non)degradable nerve conduits. The main disadvantages of this technique are the risk that nerve fibers can grow out of the muscle tissue during nerve regeneration, and that a donor site is necessary to harvest the muscle tissue. Despite publications on nerve conduits as an alternative for peripheral nerve repair, autologous nerve grafting is still the standard care for treatment of a nerve gap in the clinical situation; however, the use of the skeletal muscle tissue technique can be added to the surgeon's arsenal of peripheral nerve repair tools, especially for bridging short nerve defects or when traditional nerve autografts cannot be employed. This technique has been investigated both experimentally and clinically and, in this article, an overview of the literature on skeletal muscle grafts for bridging peripheral nerve defects is presented.
Role of a Peptide Tagging System in Degradation of Proteins Synthesized from Damaged Messenger RNA (1996)

Variants of lambda repressor and cytochrome b562 translated from messenger RNAs without stop codons were modified by carboxyl terminal addition of an ssrA-encoded peptide tag and subsequently degraded by carboxyl terminal-specific proteases present in both the cytoplasm and periplasm of Escherichia coli. The tag appears to be added to the carboxyl terminus of the nascent polypeptide chain by cotranslational switching of the ribosome from the damaged messenger RNA to ssrA RNA.
[Mechanism of photosensitized luminescence of singlet oxygen dimols in air-saturated pigment solutions]. (2010)

Luminescence of singlet oxygen dimols (1O2)2 with the main spectral maximum at 703-706 nm and much weaker bands at 640 and 770-780 nm was studied using mechanical phosphoroscopes in aerobic solutions of the nonfluorescent photosensitizer phenalenone in CCl4 and C6F6 at relatively low radiant power. The spectrum of this luminescence resembles that of dimol luminescence, which we had detected previously in solutions of porphyrins and other compounds. It was shown that, in phenalenone solutions, the mechanism of dimol luminescence involves reaction of two 1O2 molecules and one ground-state pigment molecule. It is most likely that light is emitted by the dimol-pigment contact complexes formed as a result of collisions of 1O2 with metastable, probably triplet intermediates that result from reactions of 1O2 with pigment molecules. It is proposed that this luminescence mechanism is of general importance for many organic and biologically important systems where singlet oxygen is generated. However, a comparison with the literature data suggests that the luminescence of this type can be detected at relatively low rates of 1O2 generation. At high singlet oxygen generation rates, dimol luminescence with the main maximum at 635-637 nm dominates, which is likely caused by direct collisions of 1O2 molecules.
Polyphase complementary codes (1980)

Previous work on polyphase complementary codes is reviewed, and a number of new results are presented including additional kernels and lengths. Generating methods from other binary and polyphase sequences are given and negative results of other existence searches reported. Advantages of specialized forms for radar and Loran-C are discussed, including complementary Barker codes. A table of known lengths of pairs, triads and quads of sequences is given.
Noninvasive assessment of lung volume: Respiratory inductance plethysmography and electrical impedance tomography (2005)

The promise of monitoring techniques such as RIP and EIT is that they will guide lung protective ventilation strategies and allow the clinician to optimize lung recruitment, maintain an open lung, and limit overdistension. EIT is the only bedside method that allows repeated, noninvasive measurements of regional lung volumes. In the future, it will be important to standardize the definitions of alveolar recruitment and ultimately demonstrate the superiority of EIT-guided ventilator management in providing lung protective ventilation.