gebhart/patrepeval huggingface dataset:
Exploring the physiological effects of double‐cone coil TMS over the medial frontal cortex on the anterior cingulate cortex: an H215O PET study (2007)

Transcranial magnetic stimulation (TMS) using a double-cone coil over the medial frontal cortex has the potential to clarify the function of the anterior cingulate cortex (ACC) in cognition, emotion and mood disorders. Following demonstration of disruption of performance on psychological tasks closely linked to cingulate function using this TMS technique, the current study aimed to directly measure the regional distribution of physiological effects of stimulation in the brain with H2(15)O PET. Experiment 1 assessed the effect of increasing numbers of pulse trains of TMS on regional cerebral blood flow (rCBF). Experiment 2 assessed the capacity of medial frontal TMS to modulate brain activity associated with the Stroop task using medial parietal TMS as a control site of stimulation. SPM99 analyses, using the ACC as a region of interest, revealed clusters of increased rCBF during medial frontal TMS in Brodmann area 24 and reduced rCBF in more ventral ACC, the latter occurring in both experiments. In a whole-brain analysis, striking changes in rCBF were observed distal to the ACC following medial frontal TMS. Although TMS reliably affected Stroop task performance in early trials, there was no interaction between TMS and Stroop condition in rCBF. Our results suggest that medial frontal TMS using the double-cone coil can affect ACC activity. However, a number of more distal cortical areas were also affected in these experiments. These additional changes may reflect either 'downstream' effects of altered cingulate cortex activity or direct effects of the coil.
Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor (2020)

Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.
Structure and Function of a Vimentin-associated Matrix Adhesion in Endothelial Cells (2001)

The alpha4 laminin subunit is a component of endothelial cell basement membranes. An antibody (2A3) against the alpha4 laminin G domain stains focal contact-like structures in transformed and primary microvascular endothelial cells (TrHBMECs and HMVECs, respectively), provided the latter cells are activated with growth factors. The 2A3 antibody staining colocalizes with that generated by alphav and beta3 integrin antibodies and, consistent with this localization, TrHBMECs and HMVECs adhere to the alpha4 laminin subunit G domain in an alphavbeta3-integrin-dependent manner. The alphavbeta3 integrin/2A3 antibody positively stained focal contacts are recognized by vinculin antibodies as well as by antibodies against plectin. Unusually, vimentin intermediate filaments, in addition to microfilament bundles, interact with many of the alphavbeta3 integrin-positive focal contacts. We have investigated the function of alpha4-laminin and alphavbeta3-integrin, which are at the core of these focal contacts, in cultured endothelial cells. Antibodies against these proteins inhibit branching morphogenesis of TrHBMECs and HMVECs in vitro, as well as their ability to repopulate in vitro wounds. Thus, we have characterized an endothelial cell matrix adhesion, which shows complex cytoskeletal interactions and whose assembly is regulated by growth factors. Our data indicate that this adhesion structure may play a role in angiogenesis.
Chemical vapor deposition of poly (p-phenylene vinylene) based light emitting diodes with low turn-on voltages (1997)

We report fabrication of single layer poly (p-phenylene vinylene) (PPV) light emitting diodes with low turn-on voltages by chemical vapor deposition of dihalo p-xylenes. Devices made from dibromo p-xylene exhibit turn-on fields of 2×106 V/cm, which is in good agreement with solution processed PPV devices. Devices made from dichloro p-xylene, however, have significantly lower turn-on fields of 6.5×105 V/cm. The electroluminescent output of bilayer PPV/tris (8-hydroxyquinoline) aluminum devices made from the two monomers suggests that the chlorine based polymer may have improved electron transport characteristics compared to solution processed polymer, which is tentatively attributed to residual chlorine from the thermal conversion process.
Cells in the Urine Sediment (2001)

©This article describes the various cells that may be encountered in the urine sediment. Each cell type is described in terms of the source or mechanism of formation, together with the pathologic or main clini
An assessment of the reproducibility and safety of 2-deoxy-D-glucose as a gastric acid stimulant in duodenal ulcer patients. (1975)

In studying the effects of 2-deoxy-D-glucose (2-DG) on the vagus nerve in preoperative patients with duodenal ulcer we have concluded that (1) in initiating gastric acid secretion 2-DG produces a response that is reproducible after 30 days; (2) 2-DG when given in a dose of 40 mg/kg intravenously produces a glucopenic state that appears safe in an otherwise healthy patient. We consider that 2-DG is a worthwhile agent in the investigation of the duodenal ulcer patient.
Unbalance of L-lysine flux in Corynebacterium glutamicum and its use for the isolation of excretion-defective mutants (1995)

We found that the simple addition of L-methionine to the wild type of Corynebacterium glutamicum results in excretion of the cellular building block L-lysine up to rates of 2.5 nmol/min/mg (dry weight). Biochemical analyses revealed that L-methionine represses the homoserine dehydrogenase activity and reduces the intracellular L-threonine level from 7 to less than 2 mM. Since L-lysine synthesis is regulated mainly by L-threonine (plus L-lysine) availability, the result is enhanced flux towards L-lysine. This indicates a delicate and not well controlled type of flux control at the branch point of aspartate semialdehyde conversion to either L-lysine or L-threonine, probably due to the absence of isoenzymes in C. glutamicum. The inducible system of L-lysine excretion discovered was used to isolate mutants defective in the excretion of this amino acid. One such mutant characterized in detail accumulated 174 mM L-lysine in its cytosol without extracellular excretion of L-lysine, whereas the wild type accumulated 53 mM L-lysine in the cytosol and 5.9 mM L-lysine in the medium. The mutant was unaffected in L-lysine uptake or L-isoleucine or L-glutamate excretion, and also the membrane potential was unaltered. This mutant therefore represents a strain with a defect in an excretion system for the primary metabolite L-lysine.
A 10.8 mW Body Channel Communication/MICS Dual-Band Transceiver for a Unified Body Sensor Network Controller (2009)

An energy-efficient dual-band transceiver for unified body sensor network is presented. The transceiver provides 30-70 MHz body channel communication (BCC) and 402-405 MHz medical implant communication service (MICS). For low energy consumption, the BCC and MICS band circuits in the receiver operate concurrently with their front-ends shared. As a result, up to 30% energy saving is achieved. The dual-band front-end circuits consist of a cascaded LC tank LNA and a current-recycling concurrent-down conversion mixer. The proposed LNA provides > 16 dB gains both in the BCC and MICS bands and suppresses interferences coupled through the human body by more than 10 dB. For BCC robustness, a variable adaptive frequency hopping is applied. The transceiver fabricated with 0.18 ¿m CMOS is fully compatible with the FCC regulations for MICS and consumes 10.8 mW and 4.9 mW in its RX and TX modes, respectively. The adjacent channel rejections are measured at > 30 dB in the dual-bands.
Targeting the Kinesin Spindle Protein: Basic Principles and Clinical Implications (2008)

Kinesin spindle protein (KSP), a member of the kinesin superfamily of microtubule-based motors, plays a critical role in mitosis as it mediates centrosome separation and bipolar spindle assembly and maintenance. Inhibition of KSP function leads to cell cycle arrest at mitosis with the formation of monoastral microtubule arrays, and ultimately, to cell death. Several KSP inhibitors are currently being studied in clinical trials and provide new opportunities for the development of novel anticancer therapeutics alternative from the available microtubule targeting drugs.
Role of glutamic acid decarboxylase in the prepubertal inhibition of the luteinizing hormone releasing hormone release in female rhesus monkeys (1996)

To investigate further the role of GABA in the onset of puberty, this study examines whether glutamic acid decarboxylase (GAD), the catalytic enzyme for GABA synthesis, is involved in the suppression of luteinizing hormone releasing hormone (LHRH) before puberty in rhesus monkeys. First, both GAD67 and GAD65 mRNAs were detectable by reverse transcription-PCR analysis in the preoptic area, medio-basal hypothalamus, posterior hypothalamic area, and hippocampus of the monkey brain. Second, effects of antisense oligodeoxynucleotides (D-oligos) for GAD67 and GAD65 mRNAs on LHRH release were examined in conscious female rhesus monkeys at the prepubertal stage using a push-pull perfusion method. The GAD67 or GAD65 antisense D-oligos or scrambled D-oligos were infused directly into the stalk-median eminence. Both the GAD67 and the GAD65 antisense D-oligos induced a large and prompt increase in LHRH release, whereas the scrambled D-oligos did not induce any significant effect. The results suggest that the removal of GABA inhibition by interfering with GAD synthesis is effective in increasing LHRH release in prepubertal monkeys. Third, the specificity of the antisense D-oligos on GAD levels was examined by incubating basal hypothalami with D-oligos in vitro and subsequent Western blot analysis. The antisense D-oligos consistently decreased the proteins GAD67 and GAD65 compared with respective control D-oligos. We conclude that the decrease of tonic GABAergic inhibition and maturational changes in GAD synthesis may be critical factors for the onset of puberty in nonhuman primates.
Pose Scoring by NMR (2004)

Recently, we have developed a fast approach to calculate NMR chemical shifts using the divide and conquer method at the semiempirical level. To demonstrate the utility of this approach for characterizing protein-ligand interactions, we used the deviation of calculated chemical shift perturbations from experiment to determine the orientation of a ligand (GPI-1046) in the binding pocket of the FK506 binding protein (FKBP12). Moreover, we were able to select the native state of the ligand from a collection of decoy poses. A key hydrogen bond between O1 and HN in Ile56 was also identified. Our results suggest that ligand-induced chemical shift perturbations can be used to refine protein/ligand structures.
Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine (2013)

Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine--composed of attenuated, aseptic, purified, cryopreserved PfSPZ--was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 10(5) PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.
Mechanism of Heparin Activation of Antithrombin (1998)

To determine the role of individual saccharide residues of a specific heparin pentasaccharide, denoted DEFGH, in the allosteric activation of the serpin, antithrombin, we studied the effect of deleting pentasaccharide residues on this activation. Binding, spectroscopic, and kinetic analyses demonstrated that deletion of reducing-end residues G and H or nonreducing-end residue D produced variable losses in pentasaccharide binding energy of approximately 15-75% but did not affect the oligosaccharide's ability to conformationally activate the serpin or to enhance the rate at which the serpin inhibited factor Xa. Rapid kinetic studies revealed that elimination of the reducing-end disaccharide marginally affected binding to the native low-heparin-affinity conformational state of antithrombin but greatly affected the conversion of the serpin to the activated high-heparin- affinity state, although the activated conformation was still favored. In contrast, removal of the nonreducing- end residue D drastically affected the initial low-heparin-affinity interaction so as to favor an alternative activation pathway wherein the oligosaccharide shifted a preexisiting equilibrium between native and activated serpin conformations in favor of the activated state. These results demonstrate that the nonreducing-end residues of the pentasaccharide function both to recognize the native low-heparin-affinity conformation of antithrombin and to induce and stabilize the activated high-heparin-affinity conformation. Residues at the reducing-end, however, poorly recognize the native conformation and instead function primarily to bind and stabilize the activated antithrombin conformation. Together, these findings establish an important role of the heparin pentasaccharide sequence in preferential binding and stabilization of the activated conformational state of the serpin.
Expression of the human insulin gene and cDNA in a heterologous mammalian system. (1983)

The human insulin gene or the corresponding cDNA has been inserted into the early region of a simian virus 40 vector in which all SV40 splice junctions were deleted while the early promoter and polyadenylation regions remained intact. The expression of insulin-coding sequences was tested in permissive monkey COS cells. The insulin cDNA was transcribed from the early promoter to produce a stable polyadenylated RNA which was translated, and immunoreactive human proinsulin accumulated in the medium. Thus RNA splicing is not obligatory for insulin expression in this system. The genomic insulin transcript was also initiated from the SV40 promoter and terminated at the SV40 polyadenylation site. S1 endonuclease mapping revealed that the transcript is processed via two alternative splicing pathways within the insulin gene. About one-third of the total transcripts are processed normally with removal of the two insulin-specific introns. This transcript is apparently translated normally since immunoreactive proinsulin accumulates in the medium. About two-thirds of the transcripts are processed via an alternative splicing pathway involving a new splice acceptor site located within the coding region of the insulin gene. This results in a codon frameshift such that translation would produce a novel chimeric peptide containing the insulin NH2-terminal B chain, but a different COOH terminus containing human and SV40 sequences. A peptide of the predicted size is detected in the COS cell extract.
Ti3+-, V2+/3+-, Cr2+/3+-, Mn2+-, and Fe2+-Substituted MOF-5 and Redox Reactivity in Cr- and Fe-MOF-5 (2013)

The metal nodes in metal-organic frameworks (MOFs) are known to act as Lewis acid catalysts, but few reports have explored their ability to mediate reactions that require electron transfer. The unique chemical environments at the nodes should facilitate unusual redox chemistry, but the difficulty in synthesizing MOFs with metal ions in reduced oxidation states has precluded such studies. Herein, we demonstrate that MZn3O(O2C-)6 clusters from Zn4O(1,4-benzenedicarboxylate)3 (MOF-5) serve as hosts for V(2+) and Ti(3+) ions and enable the synthesis of the first MOFs containing these reduced early metal ions, which can be accessed from MOF-5 by postsynthetic ion metathesis (PSIM). Additional MOF-5 analogues featuring Cr(2+), Cr(3+), Mn(2+), and Fe(2+) at the metal nodes can be obtained by similar postsynthetic methods and are reported here for the first time. The inserted metal ions are coordinated within an unusual all-oxygen trigonal ligand field and are accessible to both inner- and outer-sphere oxidants: Cr(2+)- converts into Cr(3+)-substituted MOF-5, while Fe(2+)-MOF-5 activates NO to produce an unusual Fe-nitrosyl complex.
Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy (2017)

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes. For example, type I IFNs drive not only the high maturation status of DCs, but also have a direct impact in cytotoxic T lymphocytes, NK cell activation, induction of tumor cell death and inhibition of angiogenesis. A variety of stimuli, including some standard cancer treatments, promote the expression of endogenous IFN-α/β, which then participates as a fundamental component of immunogenic cell death. Systemic treatment with recombinant protein has been used for the treatment of melanoma. The induction of endogenous IFN-α/β has been tested, including stimulation through pattern recognition receptors. Gene therapies involving IFN-α/β have also been described. Thus, harnessing type I IFNs as an effective tool for cancer therapy continues to be studied.
Mechanism of transmission and modulation of renal pain in cats: effects of transcutaneous electrical nerve stimulation on renal pain (1995)

Transcutaneous electrical nerve stimulation (TENS) has widely been employed as a method of obtaining analgesia in medical practice. The mechanisms of pain relief by TENS are known to be associated with the spinal gate control mechanism or descending pain inhibitory system. However, most of the studies concerning the analgesic effects and their mechanisms for TENS have dealt with somatic pain. Thus, in this experiment, we investigated the analgesic effects of TENS on renal pain as a model of visceral pain, and the characteristics of the dorsal horn cells with renal inputs. The renal pain was induced by acute occlusion of the ureter or renal artery. The main results are summarized as follows: 1) The renal nerve was composed of A beta, A delta and C fiber groups; the thresholds for each group were 400-800 mV, 1.1-1.5 V, and 2.1-5.8 V, respectively. 2) The dorsal horn cells tested received A and/or C afferent fibers from the kidney, and the more C inputs the dorsal horn cells had, the greater was the response to the stimuli that elicited the renal pain. 3) 94.9% of cells with renal input had the concomitant somatic receptive fields on the skin; the high threshold (HT) and wide dynamic range (WDR) cells exhibited a greater responses than low threshold (LT) cells to the renal pain-producing stimuli. 4) TENS reduced the C-responses of dorsal horn cells to 38.9 +/- 8.4% of the control value and the effect lasted for 10 min after the cessation of TENS. 5) By TENS, the responses evoked by acute occlusion of the ureter or renal artery were reduced to 37.5 +/- 9.7% and 46.3 +/- 8.9% of the control value, respectively. This analgesic effects lasted 10 min after TENS. 6) The responses elicited by squeezing the receptive fields of the skin were reduced to 40.7 +/- 7.9% of the control value and the effects lasted 15 min after TENS. These results suggest that most of dorsal horn cells with renal inputs have the concomitant somatic inputs and TENS can alleviate the renal pain as well as somatic pain.
Interaction of platelet-derived growth factor with its fibroblast receptor. Demonstration of ligand degradation and receptor modulation. (1982)

Platelet-derived growth factor (PDGF) has previously been shown to bind to a specific high affinity receptor on human foreskin fibroblasts. The present study was carried out to characterize some of the cellular events resulting from the interaction of the ligand with its receptor. Radiolabeled PDGF was rapidly internalized and degraded after binding to the cells. The degradation was complete and was inhibited by low concentrations of the lysosomotropic agents, chloroquine, ammonium chloride, or methylamine, suggesting that the degradation occurs in the lysosomes. The cellular binding capacity for PDGF decreased after exposure of the cells to PDGF at 37 degrees C. This down regulation of the PDGF receptor was optimal after a 60-min incubation at 37 degrees C and half-maximal at 0.5 nM concentration of PDGF. The binding capacity was restored when the PDGF-containing medium was changed to medium without PDGF; the binding capacity increased from 40 to 80% od the initial value after a 4-h incubation at 37 degrees C. The reappearance on the cell surface of PDGF-binding sites was dependent on protein synthesis and totally blocked by cycloheximide (20 micrograms/ml). Thus, either the receptor has to be resynthesized after internalization or, alternatively, any step in the recycling of "used" receptors is dependent on protein synthesis. Exposure of the cells to PDGF also caused a dose-dependent decrease in the binding capacity for epidermal growth factor which has a distinct receptor on these cells. In contrast, epidermal growth factor did not modulate the PDGF binding capacity, lending no support to the idea that the receptors for epidermal growth factor and PDGF are processed in a common pathway.
Development of Decompensated Dilated Cardiomyopathy Is Associated With Decreased Gene Expression and Activity of the Milrinone-Sensitive cAMP PhosphodiesterasePDE3A (1997)

Selective downregulation of PDE3A may account in part for the ineffectiveness of milrinone in the treatment of severe CHF.