gebhart/patrepeval huggingface dataset:
Modulation of interleukin 1 beta gene expression using antisense phosphorothioate oligonucleotides. (1990)

The production of interleukin 1 beta (IL1 beta) in lipopolysaccharide (LPS) stimulated monocytes was inhibited by 98% using antisense phosphorothioate oligonucleotides complementary to the 5' untranslated and exon 6 regions of IL1 beta mRNA. A sense phosphorothioate oligonucleotide failed to inhibit IL1 beta production. The inhibition of IL1 beta synthesis was not due to reduced cell viability and [35S]methionine incorporation showed that it could not be accounted for by an overall inhibition in protein synthesis. Tumour necrosis factor (TNF) and IL1 alpha production was also inhibited but to a lesser extent than IL1 beta. The use of antisense phosphorothioate oligonucleotides to inhibit IL1 production should enable the complex pathways of IL1 regulation to be elucidated and provide information on the biological role of these cytokines.
Regulation of the Procoagulant Response to Arterial Injury (1999)

The last few years have provided increasing evidence to support a major role for TF in the initiation and propagation of thrombosis after acute arterial injury. Although thrombotic occlusion occurs in a small minority of patients undergoing acute coronary interventions or bypass surgery, mural thrombi are likely to be present in almost all cases. These thrombi may stimulate SMC and promote the development of intimal hyperplasia and luminal narrowing. The use of inhibitors of TF and factor VIIa, therefore, may not only be valuable for inhibiting thrombus formation associated with acute arterial interventions, but may also have benefit in attenuating intimal hyperplasia. Although this paper focuses on the role of TF in establishing a procoagulant state after arterial injury, the fibrinolytic system undoubtedly plays a role in balancing the effects of increased TF production in the arterial wall. This is underscored by the success of activators of fibrinolysis (tissue plasminogen activator, streptokinase, urokinase) in revascularization in the setting of acute myocardial infarction and is reviewed elsewhere. Likewise, local regulation of TFPI in the atherosclerotic plaque and injured vessel wall may be important in attenuating the effects of increased TF synthesis and accumulation. It has been assumed that the primary source of active TF after arterial injury is either SMC or invading macrophages and that active TF is anchored to the surface of these cells. Recent data have suggested that the majority of cell-associated TF is either encrypted on the cell surface or present in an intracellular pool. Arterial injury may, therefore, involve the de-encryption of surface TF or the release of intracellular TF. In addition, active vascular TF may be present in microparticles that are not anchored to the arterial wall and may be washed into the circulation. The procoagulant state may be further accentuated by the accumulation of bloodborne TF at sites of arterial injury and in developing thrombi. This TF is likely to arise from circulating leukocytes, including neutrophils and monocytes. These studies suggest that the cellular processing of TF may be an important target for inhibiting thrombotic complications associated with arterial injury and acute coronary events.
Improving the quality factor of microwave compact resonators by optimizing their geometrical parameters (2012)

Applications in quantum information processing and photon detectors are stimulating a race to produce the highest possible quality factor on-chip superconducting microwave resonators. We have tested the surface-dominated loss hypothesis by systematically studying the role of geometrical parameters on the internal quality factors of compact resonators patterned in Nb on sapphire. Their single-photon internal quality factors were found to increase with the distance between capacitor fingers, the width of the capacitor fingers, and the resonator impedance. Quality factors were improved from 210 000 to 500 000 at T = 200 mK. All of these results are consistent with our starting hypothesis.
New nonpeptide angiotensin II receptor antagonists. 3. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)pyridine derivatives (1993)

A novel series of nonpeptide angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 3-substituted 2,6-dialkylpyridine. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.005-0.5 microM. A variety of substituents was found to be effective at the 3-position of the pyridine ring. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-1.0 mg/kg. One of the compounds, 2-ethyl-5,6,7,8-tetrahydro-4-([2'-(1H-tetrazol-5-yl)biphenyl-4y l] methoxy)quinoline (26), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg po in AII-infused, conscious, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model compound 26 showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg po. Based on its profile, this compound, designated ICI D6888, has been selected for evaluation in volunteers.
Technical Note on Microcatheter Implantation for Local Inner Ear Drug Delivery (2006)

If the pharmacokinetics or pharmacodynamics of a specific local inner ear therapy approach requires a continuous intratympanic drug application (e.g., to restore hearing in patients with severe or profound hearing loss), the temporary implantation of a microcatheter by a standardized surgical technique is a feasible and appropriately safe method for providing continuous drug delivery to the inner ear.
Soluble matrix of hen's eggshell extracts changesin vitrothe rate of calcium carbonate precipitation and crystal morphology (1996)

1. Extra and intramineral eggshell matrix proteins were solubilised before and after demineralisation by sequential extractions using guanidine hydrochloride and EDTA. 2. The intramineral electrophoretic profile of SDS-PAGE showed the presence of 80, 66, 43, 36 and 15 kDa bands with a predominance of a 17 kDa band. In the extramineral part, the major protein was the 15 kDa band. 3. The introduction of intramineral extract to a metastable solution of calcium carbonate delayed the rate of crystal growth. The delay in the rate of precipitation was elicited by a single fraction (MW 50-80 kDa), isolated by gel filtration chromatography, of eggshell extracts. Extramineral extracts had no effect. 4. Addition in vitro of intramineral eggshell extracts modified the morphology of calcite; the crystals aggregated and showed irregular surfaces. 5. These observations suggest that constituents of the eggshell matrix are involved in the control of calcite growth and crytallographic structure of the hen's eggshell.
Recombinant Leptin for Weight Loss in Obese and Lean Adults (1999)

A dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects. Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted.
Implication of Gut Immunology in the Design of Oral Vaccines (2010)

In developing countries, oral immunization is more readily accepted than parenteral, as it accompanies the ease and safety of administration and induces the desired mucosal immune response against highly infectious pathogen transmitted through mucosal routes. Despite the obvious need and apparent merits, the success in the field of oral vaccination is limited due to factors including harsh gastric environment, enzymatic barrier, intestinal epithelium barrier and the fear of oral tolerance reported in case of mucosal vaccination. The number of strategies has been focused at conquering the mucosal barrier for maximization of the intestinal uptake and stabilization of the biological at all stages before they reach their target. Although, considerable success has been attained using these strategies but none of these have achieved commercial status. Therefore a rationally designed oral vaccine should be successfully delivered to the intestinal mucosal immune cells, and induce both humoral and cellular counterparts of immunity along with the mucosal immune response. The aim of this review article is to describe the recent development in the understanding of the molecular mechanism and implication of gastrointestinal epithelium and cytokines interplay in the induction of immunity and tolerance. The review has been elaborated to discuss the rationale of design of suitable carrier in conjunction with the peculiar necessities of gastrointestinal tract for induction of well balanced immune response.
Fluorous Mixture Synthesis: A Fluorous-Tagging Strategy for the Synthesis and Separation of Mixtures of Organic Compounds (2001)

The solution-phase synthesis of organic compounds as mixtures rather than in individual pure form offers efficiency advantages that are negated by the difficulty in separating and identifying the components of the final mixture. Here, a strategy for mixture synthesis that addresses these separation and identification problems is presented. A series of organic substrates was tagged with a series of fluorous tags of increasing fluorine content. The compounds were then mixed, and multistep reactions were conducted to make enantiomers or analogs of the natural product mappicine. The resulting tagged products were then demixed by fluorous chromatography (eluting in order of increasing fluorine content) to provide the individual pure components of the mixture, which were detagged to release the final products.
Two absorption furosemide prodrugs (1999)

The structures of two absorption furosemide prodrugs, hexanoyloxymethyl 4-chloro-N-furfuryl-5-sulfamoyl-anthranilate (C19H23CIN2O7S), (I), and benzoyloxymethyl 4-chloro-N-furfuryl-5-sulfamoylanthranilate (C20H17CIN2O7S), (II), are described in this paper and compared with furosemide and four other prodrugs. The molecular conformations of both compounds are similar to those of the other prodrugs; the packing and the crystal system are the primary differences. Compound (I) crystallizes in the trigonal space group R3 and compound (II) in the monoclinic space group P2(1)/n. The packing of both structures is stabilized by a three-dimensional hydrogen-bond network.
Theory of stimulated Raman scattering cancellation in wavelength-division-multiplexed systems via spectral inversion (1999)

By exploiting the reflection symmetry of the underlying evolution equations, we theoretically demonstrate that stimulated Raman scattering crosstalk in continuous-wave wavelength-division-multiplexed systems can be totally eliminated using spectral inversion techniques. We show that this result is always true, irrespective of the shape of the Raman gain curve or the loss/gain profile along the optical fiber system. These results are illustrated by means of relevant examples.
The Conformation of Single Stranded Oligonucleotides and of Oligonucleotide-Oligopeptide Complexes from their Rotation Relaxation in the Nanosecond Time Range (1985)

The conformation of single stranded oligonucleotides is analysed by measurements of their rotation time constants. The oligomers are aligned to some degree by short electric field pulses; after pulse termination the transition to a random orientation is followed by measurements of the linear dichroism. An efficient deconvolution procedure is developed for evaluation of the experimental data obtained in the ns-time range. The increase of rotation time constants observed for chain lengths in the range from 14 to 22 residues are interpreted according to a weakly bending rod model providing a persistence length and a Stokes' diameter. The Stokes' diameters obtained for ribo- and deoxyriboadenylates are about 13A, in approximate agreement with the expectation for a single stranded helix. The persistence length L = 53A corresponding to approximately 16 nucleotide residues found for riboadenylates at 2 degrees C appears to reflect relatively strong stacking interactions at this temperature. However, a comparison with the average length of stacked residues evaluated from available thermodynamic parameters of base stacking indicate that unstacked residues are not completely flexible. Apparently the ribose-phosphate chain provides an essential contribution to the stiffness of oligomers and polymers, even when the bases are unstacked. Addition of 100 microM Mg2+ leads to an increase of the persistence length to 88A. Corresponding measurements with deoxyriboadenylates show a slightly lower value of the persistence length than that found for riboadenylates. Addition of LysTrpLys and LysTyrLys to A(pA)19 leads to an increase of the rotation time constant, which corresponds approximately to a length increment by one residue per bound peptide. Since controls performed with LysLeuLys do not show any similar effect, the increase of the time constants induced by LysTrpLys and LysTyrLys is attributed to intercalation of the aromatic amino acids.
A Peptide Inhibitor of c-Jun N-Terminal Kinase Protects against Both Aminoglycoside and Acoustic Trauma-Induced Auditory Hair Cell Death and Hearing Loss (2003)

Hearing loss can be caused by a variety of insults, including acoustic trauma and exposure to ototoxins, that principally effect the viability of sensory hair cells via the MAP kinase (MAPK) cell death signaling pathway that incorporates c-Jun N-terminal kinase (JNK). We evaluated the otoprotective efficacy of D-JNKI-1, a cell permeable peptide that blocks the MAPK-JNK signal pathway. The experimental studies included organ cultures of neonatal mouse cochlea exposed to an ototoxic drug and cochleae of adult guinea pigs that were exposed to either an ototoxic drug or acoustic trauma. Results obtained from the organ of Corti explants demonstrated that the MAPK-JNK signal pathway is associated with injury and that blocking of this signal pathway prevented apoptosis in areas of aminoglycoside damage. Treatment of the neomycin-exposed organ of Corti explants with D-JNKI-1 completely prevented hair cell death initiated by this ototoxin. Results from in vivo studies showed that direct application of D-JNKI-1 into the scala tympani of the guinea pig cochlea prevented nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity. Local delivery of D-JNKI-1 also prevented acoustic trauma-induced permanent hearing loss in a dose-dependent manner. These results indicate that the MAPK-JNK signal pathway is involved in both ototoxicity and acoustic trauma-induced hair cell loss and permanent hearing loss. Blocking this signal pathway with D-JNKI-1 is of potential therapeutic value for long-term protection of both the morphological integrity and physiological function of the organ of Corti during times of oxidative stress.
Identification of a Common Developmental Pathway for Thymic Natural Killer Cells and Dendritic Cells (1998)

Current data support the notion that the thymus is seeded by a yet uncommitted progenitor cell able to generate T cells, B cells, natural killer (NK) cells, and dendritic cells (DCs). We assess in this report the developmental relationship of DCs and NK cells derived from a small subset of CD34(+) human postnatal thymocytes that, like the earliest precursors in the fetal thymus, display low CD33 surface expression. Culture of these isolated CD34(+) CD33(lo) thymic progenitors with a mixture of cytokines, including interleukin-7 (IL-7), IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor, and stem cell factor, results in predominant generation of DCs. However, the addition of IL-2 to the cytokine mixture leads to the simultaneous development of DCs and NK cells. Both developmental pathways progress through a transient population of CD34(+)CD44(bright) CD5(lo/-)CD33(+) large-sized cells, distinct from small-sized T-lineage precursors, that contain bipotential NK/DC progenitors. These data provide evidence of linked pathways of NK cell and DC development from intrathymic precursors and suggest that NK cells and DCs branch off the T lineage through a common intermediate progenitor.
Structure of a human rhinovirus complexed with its receptor molecule. (1993)

Cryoelectron microscopy has been used to determine the structure of a virus when complexed with its glycoprotein cellular receptor. Human rhinovirus 16 complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule 1 shows that the intercellular adhesion molecule 1 binds into the 12-A deep "canyon" on the viral surface. This result confirms the prediction that the viral-receptor attachment site lies in a cavity inaccessible to the host's antibodies. The atomic structures of human rhinovirus 14 and CD4, homologous to human rhinovirus 16 and intercellular adhesion molecule 1, showed excellent correspondence with observed density, thus establishing the virus-receptor interactions.
Low-power DAC-less PAM-4 transmitter using a cascaded microring modulator (2016)

Future super-computer interconnect systems and data centers request ultrahigh data rate links at low cost and power consumption, for which transmitters with a high level of integration and spectral efficient formats are key components. We report 60 Gb/s pulse-amplitude modulation (PAM-4) of an optical signal using a dual-microring silicon photonics circuit, making a low-power, digital-to-analog converter (DAC)-less PAM modulator. The power consumption is evaluated below 100 fJ/bit, including thermal adjustments. To the best of our knowledge, these results feature the lowest reported power consumption for PAM signaling in a DAC-less scheme for data rate beyond 40 Gb/s.
A computational model of binaural localization and separation (2005)

Multiple sound signals, such as speech and interfering noises, can be fairly well separated, localized, and interpreted by human listeners with normal binaural hearing. The computational model presented here, based on earlier cochlear modeling work, is a first step at approaching human levels of performance on the localization and separation tasks. This combination of cochlear and binaural models, implemented as real-time algorithms, could provide the front end for a robust sound interpretation system such as a speech recognizer. The cochlear model used is basically a bandpass filterbank with frequency channels corresponding to places on the basilar membrane; filter outputs are half-wave rectified and amplitude-compressed, maintaining fine time resolution. In the binaural model, outputs of corresponding frequency channels from the two ears are combined by cross-correlation. Peaks in the short-time cross-correlation functions are then interpreted as direction. With appropriate preprocessing, the correlation peaks integrate cues based on signal phase, envelope modulation, onset time, and loudness. Based on peaks in the correlation functions, sources can be recognized, localized, and tracked. Through quickly varying gains, sound fragments are separated into streams representing different sources. Preliminary tests of the algorithms are very encouraging.
Preparation of Co–Fe–P amorphous fine needles with anodization technique and measurement of demagnetizing factor (1996)

The amorphous Co–Fe–P and crystalline Co fine needles with diameter 0.1–0.2 μm aspect ratio more than 100 were prepared successfully by applying the dc electrodeposition to the anodization technique and their demagnetizing factors were measured. It was found that the demagnetizing factor of film with needles decreases with increasing aspect ratio and tends to take low constant values around 0.07–0.08. To obtain the low demagnetizing factor by using the shape anisotropy of needle, it was estimated that the aspect ratio more than 100 is needed. The equivalent demagnetizing factor defined by a ratio of a field needed to achieve saturation to the averaged flux density is estimated around 0.6 for the film with Co–Fe–P amorphous needles with 0.1 μm diameter.
Cullin E3 Ligases and Their Rewiring by Viral Factors (2014)

The ability of viruses to subvert host pathways is central in disease pathogenesis. Over the past decade, a critical role for the Ubiquitin Proteasome System (UPS) in counteracting host immune factors during viral infection has emerged. This counteraction is commonly achieved by the expression of viral proteins capable of sequestering host ubiquitin E3 ligases and their regulators. In particular, many viruses hijack members of the Cullin-RING E3 Ligase (CRL) family. Viruses interact in many ways with CRLs in order to impact their ligase activity; one key recurring interaction involves re-directing CRL complexes to degrade host targets that are otherwise not degraded within host cells. Removal of host immune factors by this mechanism creates a more amenable cellular environment for viral propagation. To date, a small number of target host factors have been identified, many of which are degraded via a CRL-proteasome pathway. Substantial effort within the field is ongoing to uncover the identities of further host proteins targeted in this fashion and the underlying mechanisms driving their turnover by the UPS. Elucidation of these targets and mechanisms will provide appealing anti-viral therapeutic opportunities. This review is focused on the many methods used by viruses to perturb host CRLs, focusing on substrate sequestration and viral regulation of E3 activity.
Near-infrared laser welding of aortic and skin tissues and microscopic investigation of welding efficacy (2003)

<i>Ex vivo</i> specimens of human and porcine aorta and skin were welded using either Cr<sup>4+</sup>:YAG or Erbium fiber lasers tuned to the water absorption band at 1440-1460 nm. Welding was performed without the use of protein solders or glues. Welding efficacy was monitored by measuring the tensile strength of the welded tissue and the extent of collateral tissue damage. Full thickness tissue bonding with no collateral damage was observed with porcine aorta samples. The optimum tensile strength for porcine and human aorta was 1.33 ± 0.15 kg/cm<sup>2</sup> and 1.13 ± 0.27 kg/cm<sup>2</sup> respectively for welding at 1460 nm, while that for porcine and human skin was 0.94 ± 0.15 kg/cm<sup>2</sup> and 1.05 ± 0.19 kg/cm<sup>2</sup> respectively achieved with welding at 1455 nm. The weld strength as a function of laser wavelength demonstrated a correlation with the absorption spectrum of native water suggests that absorption of light by water in the tissue plays a significant role in laser tissue welding.