gebhart/patrepeval huggingface dataset:
Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex®, a Cannabis‐Based Medicine (2007)

Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times. This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex). Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile. No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients' quality of life.
Two-dimensional depth-resolved Mueller matrix of biological tissue measured with double-beam polarization-sensitive optical coherence tomography (2002)

A double-beam polarization-sensitive system based on optical coherence tomography was built to measure the Mueller matrix of scattering biological tissue with high spatial resolution. The Jones matrix of a sample can be determined with a single scan and subsequently converted into an equivalent nondepolarizing Mueller matrix. As a result, the system can be used to measure the Mueller matrix of an unstable sample, such as soft tissue. The polarization parameters of a porcine tendon, including magnitude and orientation of birefringence and diattenuation, were extracted by decomposition of the measured Mueller matrix.
Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia (2008)

The glycine cleavage system catalyzes the following reversible reaction: Glycine + H(4)folate + NAD(+) <==> 5,10-methylene-H(4)folate + CO(2) + NH(3) + NADH + H(+)The glycine cleavage system is widely distributed in animals, plants and bacteria and consists of three intrinsic and one common components: those are i) P-protein, a pyridoxal phosphate-containing protein, ii) T-protein, a protein required for the tetrahydrofolate-dependent reaction, iii) H-protein, a protein that carries the aminomethyl intermediate and then hydrogen through the prosthetic lipoyl moiety, and iv) L-protein, a common lipoamide dehydrogenase. In animals and plants, the proteins form an enzyme complex loosely associating with the mitochondrial inner membrane. In the enzymatic reaction, H-protein converts P-protein, which is by itself a potential alpha-amino acid decarboxylase, to an active enzyme, and also forms a complex with T-protein. In both glycine cleavage and synthesis, aminomethyl moiety bound to lipoic acid of H-protein represents the intermediate that is degraded to or can be formed from N(5),N(10)-methylene-H(4)folate and ammonia by the action of T-protein. N(5),N(10)-Methylene-H(4)folate is used for the biosynthesis of various cellular substances such as purines, thymidylate and methionine that is the major methyl group donor through S-adenosyl-methionine. This accounts for the physiological importance of the glycine cleavage system as the most prominent pathway in serine and glycine catabolism in various vertebrates including humans. Nonketotic hyperglycinemia, a congenital metabolic disorder in human infants, results from defective glycine cleavage activity. The majority of patients with nonketotic hyperglycinemia had lesions in the P-protein gene, whereas some had mutant T-protein genes. The only patient classified into the degenerative type of nonketotic hyperglycinemia had an H-protein devoid of the prosthetic lipoyl residue. The crystallography of normal T-protein as well as biochemical characterization of recombinants of the normal and mutant T-proteins confirmed why the mutant T-proteins had lost enzyme activity. Putative mechanisms of cellular injuries including those in the central nervous system of patients with nonketotic hyperglycinemia are discussed.
Methylosin A und B, Pigmente aus Methylosinus trichosporium (1983)

Screening for methanotrophic bacteria led to the isolation of a Methylosinus trichosporium strain which was characterized by the ability to produce a bright red‐violet pigment, which was found to be nearly insoluble in water. This communication reports on the formation, isolation, and purification of the pigment and its separation into the components methylosin A and B. By comparison of physico‐chemical parameters we identified the pigment as a prodiginine‐type compound. The chemical constitution of methylosin B was established. To our knowledge this is the first observation of prodiginine‐type compounds to be metabolites of methanotrophic bacteria.
Identification of Epitopes Recognized by Monoclonal Antibodies SM1 and SM2 Which React with All Pili of Neisseria gonorrhoeae but Which Differentiate between Two Structural Classes of Pili Expressed by Neisseria meningitidis and the Distribution of Their Encoding Sequences in the Genomes of Neisseria spp. (1989)

The pili expressed by all isolates of Neisseria gonorrhoeae react with two monoclonal antibodies, SM1 and SM2. In contrast, although many isolates of Neisseria meningitidis also express pili (class I) which react with antibodies SM1 and SM2, a proportion express pili (class II) which fail to react. In order to define the epitopes recognized by these antibodies, a series of overlapping peptides corresponding to the amino acid sequence of conserved regions of gonococcal pili have been synthesized. The minimum epitope recognized by antibody SM1 was found to comprise a linear peptide EYYLN, corresponding to residues 49-53 of mature pilin. In contrast, antibody SM2 reacted with a number of peptides from around the cysteine residue (Cys 1) at position 120, suggesting that an extended region may contribute to a conformational epitope recognized by this antibody in the native protein. The identification of the two epitopes defines structural differences between the classes of pili expressed by meningococci. In order to determine the distribution of pilin gene sequences in Neisseria we used as hybridization probes an oligonucleotide (PS1) with the sequence 5'-GAGTATTACCTGAATCA-3' which spans the coding region for the SM1 epitope, and a fragment of the 3' end of the gonococcal pilE gene which contains conserved sequences flanking the two Cys codons and encodes the SM2 epitope. All strains of N. gonorrhoeae and N. meningitidis tested, regardless of piliation phenotype, harboured DNA sequences homologous to those encoding the carboxy-terminus of meningococcal class I pilin. Furthermore, all gonococci and all meningococci producing class I pili hybridized with oligonucleotide probe PS1. Non-reverting non-piliated derivatives of previously class I pilus-producing strains showed reduced hybridization signals with this probe, but nevertheless retained sequences homologous to the coding sequence for the SM1 epitope. However, meningococci producing class II pili could be divided into two groups on the basis of their reaction with the PS1 probe: half the strains tested failed to react, which is consistent with our previous analysis of silent class I pilin sequences; the remainder reacted (relatively weakly) with the probe, suggesting that the silent pil sequences in these strains extend further towards the 5' end of the pilin gene than in strains studied previously. Some strains of Neisseria lactamica reacted weakly with both types of probe but failed to produce SM1-reactive pili. In contrast, isolates of Neisseria flava, Neisseria pharyngis, Neisseria sicca and a series of unrelated bacteria failed to react with both SM1 antibody and the DNA probes. This confirms that possession of 'gonococcal' pilin sequences is limited to the pathogenic neisseriae.
Energetic particle bombardment of films during magnetron sputtering (1989)

The flux of energetic, neutral particles bombarding the sample location during magnetron sputtering has been measured for several cathode–gas systems of general interest. The technique used a differentially pumped detector placed at the sample location, from 5 to 9 cm from the cathode. The detector screens out charged particles, and measures the secondary electrons produced by energetic neutral bombardment of a collector coated with a thin film of cathode material. The energetic neutral flux has been measured as a function of chamber pressure over a range of 5 to 30 mTorr, as a function of discharge power, and as a function of angle (up to 30°) for cathodes of Ti, Cu, Al, Mo, T, and W, in Ar, Ne, and Kr gases. The deposition rate of the film was measured by means of a quartz-crystal oscillator adjacent to the detector. The magnitude of the arriving, energetic neutral flux increased with decreasing gas mass or increasing cathode mass, as expected. The energetic neutral flux was found to increase with decreasing pressure, but the ratio of energetic neutrals to condensing films atoms was found to decrease slightly with decreasing pressure. The arrival rate of energetic neutrals ranged from 2–4% of the depositing atom flux for Ar+→Cu to 12%–20% for Ar+→Ti to 27%–50% for Ne+→Ta. At high discharge powers, the relative arrival rates were higher, due to gas rarefaction in the near cathode region.
Assessment of microbial diversity in human colonic samples by 16S rDNA sequence analysis (2002)

Abstract The bacterial species diversity of three colonic tissue samples from elderly people was investigated by sequence analysis of randomly cloned eubacterial 16S rDNA. The majority of sequences (87%) clustered within three bacterial groups: (1) Bacteroides; (2) low G+C content Gram-positives related to Clostridium coccoides (cluster XIVa); (3) Gram-positives related to Clostridium leptum (cluster IV). These groups have been shown to dominate the human faecal flora. Only 25% of sequences were closely related (>97%) to current species type strains, and 28% were less than 97% related to any database entry. 19% of sequences were most closely related to recently isolated butyrate-producing bacteria belonging to clusters XIVa and IV, with a further 18% of the sequences most closely related to Ruminococcus obeum and Ruminococcus torques (members of cluster XIVa). These results provide the first molecular information on the microbial diversity present in human colonic samples.
Oscillations in local field potentials of the primate motor cortex during voluntary movement. (1993)

We investigated the occurrence and distribution of oscillatory activity in local field potentials (LFPs) recorded from the frontal motor cortex of behaving monkeys performing skilled voluntary movements. LFPs were recorded simultaneously from up to 12 sites distributed throughout motor cortex while monkeys performed a visually guided, instructed delay task using the wrist or digits. Oscillatory activity between 15 and 50 Hz was evident in the LFP recorded from both primary motor cortex and premotor areas. Oscillations occurred preferentially before the visual cue to initiate movement but were infrequent during movement. Oscillations typically stopped before movement initiation during the wrist task, although they often continued into the initial phases of movement during the digit task. The relationship of oscillations to task performance was consistent across trials over periods of many months, although the amplitude and duration of oscillations varied across trials and days. Interactions between pairs of LFP recordings, evaluated with cross-correlation analysis, revealed synchronous oscillations over long distances (> 7 mm) and across primary motor cortex and premotor recording sites. These studies demonstrate that oscillations recorded in the LFP in motor cortex during trained motor tasks are not related to the details of movement execution but may be related to aspects of movement preparation.
Micromotor Pills as a Dynamic Oral Delivery Platform (2018)

Tremendous progress has been made during the past decade toward the design of nano/micromotors with high biocompatibility, multifunctionality, and efficient propulsion in biological fluids, which collectively have led to the initial investigation of in vivo biomedical applications of these synthetic motors. Despite these recent advances in micromotor designs and mechanistic research, significant effort is needed to develop appropriate formulations of micromotors to facilitate their in vivo administration and thus to better test their in vivo applicability. Herein, we present a micromotor pill and demonstrate its attractive use as a platform for in vivo oral delivery of active micromotors. The micromotor pill is comprised of active Mg-based micromotors dispersed uniformly in the pill matrix, containing inactive (lactose/maltose) excipients and other disintegration-aiding (cellulose/starch) additives. Our in vivo studies using a mouse model show that the micromotor pill platform effectively protects and carries the active micromotors to the stomach, enabling their release in a concentrated manner. The micromotor encapsulation and the inactive excipient materials have no effects on the motion of the released micromotors. The released cargo-loaded micromotors propel in gastric fluid, retaining the high-performance characteristics of in vitro micromotors while providing higher cargo retention onto the stomach lining compared to orally administrated free micromotors and passive microparticles. Furthermore, the micromotor pills and the loaded micromotors retain the same characteristics and propulsion behavior after extended storage in harsh conditions. These results illustrate that combining the advantages of traditional pills with the efficient movement of micromotors offer an appealing route for administrating micromotors for potential in vivo biomedical applications.
Wireless impedance measurements for monitoring peripheral vascular disease (2014)

Wireless microdevices powered by ultrasound energy have been fabricated to measure and telemeter tissue impedance spectrums for applications in peripheral vascular disease monitoring. The system is characterized by simplicity of the implant consisting of only two electrical components. Ex vivo testing shows the potential for constructing tissue impedance spectrum plots over the range from 10 Hz to 10 kHz by a device less than 1 mm in diameter and 1 cm long. The neurostimulator microdevice was powered by continuous waveform 650 kHz ultrasound with a swept-frequency amplitude modulation. The system was operated at safe ultrasound power levels on the order of 10-100 mW/cm(2). The device proved to be sensitive and able to measure tissue impedances over a broad range. Volume conducted signals carrying impedance information from the microdevice were remotely detected by surface biopotential electrodes.
NT5E Mutations and Arterial Calcifications (2011)

We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification. (Funded by the National Human Genome Research Institute and the National Heart, Lung, and Blood Institute of the National Institutes of Health.).
Transmembrane-truncated αvβ3 integrin retains high affinity for ligand binding: evidence for an ‘inside-out’ suppressor? (1998)

The molecular mechanisms of alphavbeta3 integrin affinity regulation have important biological implications in tumour development, wound repair and angiogenesis. We expressed, purified and characterized recombinant forms of human alphavbeta3 (r-alphavbeta3) and compared the activation state of these with alphavbeta3 in its cellular environment. The ligand specificity and selectivity of recombinant full-length and double transmembrane truncations of r-alphavbeta3 cloned in BacPAK6 vectors and expressed in Sf9 and High Five insect cells were compared with those of native placental alphavbeta3 and the receptor in situ on the cell surface. r-alphavbeta3 integrins were purified by affinity chromatography from detergent extracts of cells (full-length), and from the culture medium of cells expressing double-truncated r-alphavbeta3. r-alphavbeta3 had the same epitopes, ligand-binding specificities, bivalent cation requirements and susceptibility to RGD-containing peptides as native alphavbeta3. On M21-L4 melanoma cells, alphavbeta3 mediated binding to vitronectin, but not to fibrinogen unless activated with Mn2+. Non-activated alphaIIbbeta3 integrin as control in M21-L-IIb cells had the opposite profile, mediating binding to fibrinogen, but not to vitronectin unless activated with Mn2+. Thus these receptors had moderate to low ligand affinity. In marked contrast, purified alphavbeta3 receptors, with or without transmembrane and cytoplasmic domains, were constitutively of high affinity and able to bind strongly to vitronectin, fibronectin and fibrinogen under physiological conditions. Our data suggest that, in contrast with the positive regulation of alphaIIbbeta3 in situ, intracellular controls lower the affinity of alphavbeta3, and the cytoplasmic domains may act as a target for negative regulators of alphavbeta3 activity.
Coriacenins:  A New Class of Long Alkyl Chain Amino Alcohols from the Mediterranean Sponge Clathrina coriacea (1996)

The Mediterranean sponge Clathrina coriacea contains a series of long chain amino alcohols, named coriacenins (2−6), belonging to a new class of alkaloids. The structures of the novel compounds were elucidated by studying, with a combination of spectral and chemical methods, their peracetyl derivatives (2a−6a). Coriacenins are characterized by a bis(1,3-diamino-2-propanol) moiety and a linear alkyl chain varying both by length and by degree of unsaturation. The biosynthetic pathway leading to coriacenins seems to be unprecedented. It should, however, occur through condensation of an acetogenin with an uncommon amino acid.
Chlorosilanols ‐ more stable than you think ‐Shown with 29 Si NMR (1993)

The chlorosilanols ClnSi(OH)4-n (n = 3 … 1) can be seen by 29Si NMR spectroscopy during a partial hydrolysis-condensation of silicon tetrachloride in the NMR tube.
Cytochrome b gene sequence and structure of Pyrenophora teres and P. tritici‐repentis and implications for QoI resistance (2007)

Abstract Resistance to QoI fungicides in Pyrenophora teres (Dreschsler) and P. tritici‐repentis (Died.) Dreschsler was detected in 2003 in France and in Sweden and Denmark respectively. Molecular analysis revealed the presence of the F129L mutation in resistant isolates of both pathogens. In 2004, the frequency of the F129L mutation in populations of both pathogens further increased. The G143A mutation was also detected in a few isolates of P. tritici‐repentis from Denmark and Germany. In 2005, the F129L mutation in P. teres increased in frequency and geographical distribution in France and the UK but remained below 2% in Germany, Switzerland, Belgium and Ireland. In P. tritici‐repentis , both mutations were found in a significant proportion of the isolates from Sweden, Denmark and Germany. The G143A mutation conferred a significantly higher level of resistance (higher EC 50 values) to Qo inhibitors (QoIs) than did the F129L mutation. In greenhouse trials, resistant isolates with G143A were not well controlled on plants sprayed with recommended field rates, whereas satisfactory control of isolates with F129L was achieved. For the F129L mutation, three different single nucleotide polymorphisms (SNPs), TTA, TTG and CTC, can code for L (leucine) in P. teres , whereas only the CTC codon was detected in P. tritici‐repentis isolates. In two out of 250 isolates of P. tritici‐repentis from 2005, a mutation at position 137 (G137R) was detected at very low frequency. This mutation conferred similar resistance levels to F129L. The structure of the cytochrome b gene of P. tritici‐repentis is significantly different from that of P. teres : an intron directly after amino acid position 143 was detected in P. teres which is not present in P. tritici‐repentis . This gene structure suggests that resistance based on the G143A mutation may not occur in P. teres because it is lethal. No G143A isolates were found in any P. teres populations. Although different mutations may evolve in P. tritici‐repentis , the G143A mutation will have the strongest impact on field performance of QoI fungicides. Copyright © 2007 Society of Chemical Industry
A Mechanism for Ion Selectivity in Potassium Channels: Computational Studies of Cation-π Interactions (1993)

A combination of computational methods has been used to evaluate the interaction between the pi face of a benzene molecule and the monovalent cations of lithium, sodium, potassium, and rubidium. In the gas phase, the ions are strongly bound, and the affinity for benzene follows the expected electrostatic trend (lithium, largest; rubidium, smallest). However, in an aqueous environment, a reordering occurs such that the potassium ion is preferred over all the other ions for 2:1 benzene:ion complexes. The selectivity sequence parallels that seen in voltage-gated potassium channels. Given that several conserved aromatic residues are present in the pore region of such channels, these results suggest that the cation-pi interaction may be responsible for the ion selectivity in potassium channels.
Growth inhibition of K-ras-expressing tumours by a new vinca alkaloid, conophylline, in nude mice. (1996)

Conophylline, a new vinca alkaloid isolated from the plant Ervatamia microphylla induced normal flat morphology in K-ras-NRK and K-ras-NIH cell lines, and lowered the increased uptake of 2-deoxyglucose in K-ras-NRK cells. Conophylline inhibited the growth of K-ras-NRK cells, but this inhibition was reversible. The alkaloid also inhibited the growth of K-ras-NRK and K-ras-NIH3T3 tumours transplanted into nude mice. On the other hand, it showed no effect on survival of the mice loaded with L1210 leukaemia. Thus, conophylline is a new antitumour vinca alkaloid that induced normal phenotypes in ras-expressing cells.
Synthesis and characterization of ubiquitin ethyl ester, a new substrate for ubiquitin carboxyl-terminal hydrolase (1986)

A new substrate for ubiquitin carboxyl-terminal hydrolase, the carboxyl-terminal ethyl ester of ubiquitin, has been synthesized by a trypsin-catalyzed transpeptidation. In the presence of 1.6 M glycylglycine ethyl ester, trypsin removes the carboxyl-terminal glycylglycine of ubiquitin and replaces it with the dipeptide ester. The equilibrium mixture under these conditions contains 30% ubiquitin ethyl ester and 70% hydrolysis product, the 74-residue fragment of ubiquitin. Ubiquitin ethyl ester can be purified by gel filtration and ion-exchange chromatography. The structure of this product has been verified by identification of the products of base hydrolysis, tryptic cleavage in aqueous solution, and peptide mapping. When ubiquitin ethyl ester is incubated with purified ubiquitin carboxyl-terminal hydrolase, specific cleavage of the ester linkage is observed. A rapid, sensitive assay is described utilizing high-performance liquid chromatography. By use of this assay, it has been shown that ubiquitin carboxyl-terminal hydrolase is inactivated in the absence of thiols. Optimal protective effects are seen with 10 mM dithiothreitol. The rate of catalysis is maximal at pH 8.5, with evidence for catalytically important groups with pK values of 5.2, 7.6, and 9.5. These findings are consistent with the participation of a thiol group in the active site. Native ubiquitin is a competitive inhibitor of ubiquitin ethyl ester hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)