gebhart/patrepeval huggingface dataset:
Harnessing cerebrospinal fluid circulation for drug delivery to brain tissues (2021)

Initially thought to be useful only to reach tissues in the immediate vicinity of the CSF circulatory system, CSF circulation is now increasingly viewed as a viable pathway to deliver certain therapeutics deeper into brain tissues. There is emerging evidence that this goal is achievable in the case of large therapeutic proteins, provided conditions are met that are described herein. We show how fluid dynamic modeling helps predict infusion rate and duration to overcome high CSF turnover. We posit that despite model limitations and controversies, fluid dynamic models, pharmacokinetic models, preclinical testing, and a qualitative understanding of the glymphatic system circulation can be used to estimate drug penetration in brain tissues. Lastly, in addition to highlighting landmark scientific and medical literature, we provide practical advice on formulation development, device selection, and pharmacokinetic modeling. Our review of clinical studies suggests a growing interest for intra-CSF delivery, particularly for targeted proteins.
Regularized higher‐order in vivo shimming (2002)

A regularized algorithm is presented for localized in vivo shimming. The technique uses first- (X,Y,Z), second- (Z(2), ZX, ZY, X(2)-Y(2), XY), and third-order (Z(3)) shim coils, and is robust when applied to arbitrarily-shaped, as well as off-center, regions of interest (ROIs). A single-shot spiral pulse sequence is used for rapid field map acquisition, and a least-squares calculation of the shim currents is performed to minimize the root-mean-square (RMS) value of the B(0) inhomogeneity over a user-selected ROI. The use of a singular value decomposition (SVD) in combination with a regularization algorithm significantly improves the numerical stability of the least-squares fitting procedure. The fully automated shimming package is implemented on a 3 T GE Signa system and its robust performance is demonstrated in phantom and in vivo studies.
BYPASS EFFECT IN HIGH PERFORMANCE HEAT SINKS (2000)

Studies using commercial computational fluid dynamics software, running on a supercomputer, were carried out to investigate the effects of fin density, inlet duct velocity, and clearance area ratio, on the extent of flow bypass and its impact on the thermal performance of the heat sink. Flow bypass was found to increase with increasing fin density and clearance, while remaining relatively insensitive to inlet duct velocity. An optimum geometry, for a fixed inlet duct velocity, bypass clearance, fixed heat sink volume, and constant thickness, was determined.
Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data (2015)

Analysis of Hi-C data has shown that the genome can be divided into two compartments called A/B compartments. These compartments are cell-type specific and are associated with open and closed chromatin. We show that A/B compartments can reliably be estimated using epigenetic data from several different platforms: the Illumina 450 k DNA methylation microarray, DNase hypersensitivity sequencing, single-cell ATAC sequencing and single-cell whole-genome bisulfite sequencing. We do this by exploiting that the structure of long-range correlations differs between open and closed compartments. This work makes A/B compartment assignment readily available in a wide variety of cell types, including many human cancers.
Broad wavelength modulating and design of organic white diode based on lighting by using exciplex emission from mixed acceptors (2006)

Modulating electroluminescent (EL) spectra from interfacial exciplex emissions were observed by varying the ratios of two acceptors of exciplex-type devices in which the emissive wavelengths were tuned from 530to656nm. In the devices 4,4′,4″-tris[3-methyl-pheny(phenyl)amino]triphenylamine and (bathocuproine: scdolinium-(dibenzoyl-methane)3bathophenyl-phenathroline) mixtures were used as donor and acceptor materials, respectively. In terms of the exciplex broad band emission a white organic light emitting diode was demonstrated by skillfully designing the structure when blue subband was subjoined in the white spectrum. The white device behaves the Commission Internationale de l’Eclairage coordinates of (0.32, 0.35) with higher color stability at various biases, a color rendering index of 90.4, and a maximum luminance of 425cd∕m2, respectively, although the EL efficiency needs to be further improved. The emission mechanism of the broad exciplex band formed by two mixed acceptors was also discussed.
Interleukin (IL)-22, a Novel Human Cytokine That Signals through the Interferon Receptor-related Proteins CRF2–4 and IL-22R (2000)

We report the identification of a novel human cytokine, distantly related to interleukin (IL)-10, which we term IL-22. IL-22 is produced by activated T cells. IL-22 is a ligand for CRF2-4, a member of the class II cytokine receptor family. No high affinity ligand has yet been reported for this receptor, although it has been reported to serve as a second component in IL-10 signaling. A new member of the interferon receptor family, which we term IL-22R, functions as a second component together with CRF2-4 to enable IL-22 signaling. IL-22 does not bind the IL-10R. Cell lines were identified that respond to IL-22 by activation of STATs 1, 3, and 5, but were unresponsive to IL-10. In contrast to IL-10, IL-22 does not inhibit the production of proinflammatory cytokines by monocytes in response to LPS nor does it impact IL-10 function on monocytes, but it has modest inhibitory effects on IL-4 production from Th2 T cells.
Efficacy of Monoclonal Antibodies against Defined Antigens for Passive Immunotherapy of Chronic Gastrointestinal Cryptosporidiosis (2002)

Cryptosporidium parvum is an important cause of diarrhea in humans and calves and can persistently infect immunocompromised hosts. Presently, there are no consistently effective parasite-specific drugs for cryptosporidiosis. We hypothesized that neutralizing monoclonal antibodies (MAbs) targeting the apical complex and surface antigens CSL, GP25-200, and P23 could passively immunize against cryptosporidiosis. We recently reported that a formulation of MAbs 3E2 (anti-CSL), 3H2 (anti-GP25-200), and 1E10 (anti-P23) provided significant additive prophylactic efficacy over that of the individual MAbs in neonatal ICR mice. In the present study, these MAbs were evaluated for therapeutic efficacy against persistent infection in adult gamma interferon-depleted SCID mice. 3E2 demonstrated the most significant and consistent therapeutic effect, reducing intestinal infection in two experiments. In one experiment, 3E2 plus 3H2 and 3E2 plus 3H2 plus 1E10 also significantly reduced infection; however, no significant increase in efficacy over 3E2 alone was apparent. The results indicate that anti-CSL MAb 3E2 has highly significant efficacy in reducing, but not eliminating, persistent C. parvum infection.
Mechanical Characterization of Sol–Gel‐Derived Silicon Oxycarbide Glasses (1996)

Silicon oxycarbide glasses have been fabricated, in the shape of thin rods suitable for flexural test experiments, by pyrolysis in an inert atmosphere at 1000° and 1200°C of solgel precursors containing Si–CH 3 and Si–H bonds. The amount of carbon in the silicon oxycarbide network has been controlled by varying the carbon load in the precursor gel. Density and surface area analysis revealed that all of the samples pyrolyzed at 1200°C were well‐densified silicon oxycarbide glasses whereas for the glasses treated at 1000°C, compositions with low carbon loads showed the presence of a residual fine porous phase. The elastic modulus ( E ), flexural strength (MOR), and Vickers hardness ( H v ) increase markedly with the amount of carbon in the oxycarbide glasses reaching the maximum values ( E ∼ 115 GPa, MOR ∼ 550 MPa, and H v ∼ 9 GPa) for samples with the highest carbon content. The experimental elastic modulus values of the silicon oxycarbide glasses compare well with the theoretical estimations obtained using the Voigt and Reuss models assuming the disordered network formed by the corresponding thermodynamic compositions.
A Versatile Synthesis of Four-, Five-, and Six-membered Cyclic Ketones Using Methyl Methylthiomethyl Sulfoxide (1984)

Abstract Cyclization of 1,n-dihalo[or bis(tosyloxy)]alkanes with methyl methylthiomethyl sulfoxide in the presence of a base (n-BuLi or KH) gave three-, four-, five-, and six-membered 1-methylsulfinyl-1-methylthiocycloalkanes. These cyclization products were easily converted to the corresponding ketones by acid hydrolysis except 1-methylsulfinyl-1-methylthiocyclopropane which afforded a complicated mixture. The combination of the cyclization with the acid hydrolysis thus provides a new method for synthesizing four-, five-, and six-membered cycloalkanones. Several representative preparations, such as those of substituted cyclobutanones, 3-cyclopentenone, and tetrahydro-4-pyrone, are described.
Colloidal subwavelength nanostructures for antireflection optical coatings (2005)

A two-dimensional (2D) subwavelength nanostructure for antireflection coating is fabricated upon a transparent substrate. Self-assembled 2D colloidal crystals are used as a nanoscale composite material with controlled thickness and low refractive index. The feature size of the structure is approximately 105 nm. The structure is used for antireflection coating, and the measured reflectivity of a glass substrate is reduced to 0.3%. Enhanced transmission through the substrate is also observed.
Transgenic Tobacco and Arabidopsis Plants Expressing the Two Multifunctional Sorghum Cytochrome P450 Enzymes, CYP79A1 and CYP71E1, Are Cyanogenic and Accumulate Metabolites Derived from Intermediates in Dhurrin Biosynthesis (2000)

Novel cyanogenic plants have been generated by the simultaneous expression of the two multifunctional sorghum (Sorghum bicolor [L.] Moench) cytochrome P450 enzymes CYP79A1 and CYP71E1 in tobacco (Nicotiana tabacum cv Xanthi) and Arabidopsis under the regulation of the constitutive 35S promoter. CYP79A1 and CYP71E1 catalyze the conversion of the parent amino acid tyrosine to p-hydroxymandelonitrile, the aglycone of the cyanogenic glucoside dhurrin. CYP79A1 catalyzes the conversion of tyrosine to p-hydroxyphenylacetaldoxime and CYP71E1, the subsequent conversion to p-hydroxymandelonitrile. p-Hydroxymandelonitrile is labile and dissociates into p-hydroxybenzaldehyde and hydrogen cyanide, the same products released from dhurrin upon cell disruption as a result of pest or herbivore attack. In transgenic plants expressing CYP79A1 as well as CYP71E1, the activity of CYP79A1 is higher than that of CYP71E1, resulting in the accumulation of several p-hydroxyphenylacetaldoxime-derived products in the addition to those derived from p-hydroxymandelonitrile. Transgenic tobacco and Arabidopsis plants expressing only CYP79A1 accumulate the same p-hydroxyphenylacetaldoxime-derived products as transgenic plants expressing both sorghum cytochrome P450 enzymes. In addition, the transgenic CYP79A1 Arabidopsis plants accumulate large amounts of p-hydroxybenzylglucosinolate. In transgenic Arabidopsis expressing CYP71E1, this enzyme and the enzymes of the pre-existing glucosinolate pathway compete for the p-hydroxyphenylacetaldoxime as substrate, resulting in the formation of small amounts of p-hydroxybenzylglucosinolate. Cyanogenic glucosides are phytoanticipins, and the present study demonstrates the feasibility of expressing cyanogenic compounds in new plant species by gene transfer technology to improve pest and disease resistance.
cGMP mediates the vascular and platelet actions of nitric oxide: confirmation using an inhibitor of the soluble guanylyl cyclase. (1996)

The L-arginine:nitric oxide (NO) pathway is believed to exert many of its physiological effects via stimulation of the soluble guanylyl cyclase (SGC); however, the lack of a selective inhibitor of this enzyme has prevented conclusive demonstration of this mechanism of action. We have found that the compound 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) inhibits the elevation of cGMP induced by the NO donor S-nitroso-DL-penicillamine in human platelets and rat vascular smooth muscle (IC50 = 10-60 nM and <10 nM, respectively) and that this is accompanied by prevention of the platelet inhibitory and vasodilator actions of NO donors. ODQ also inhibited the antiaggregatory action of NO generated by the platelets but did not affect the action of prostacyclin or that of a cGMP mimetic. In addition, ODQ inhibited the vasodilator actions of endogenously released NO and of NO generated after induction of NO synthase in vascular preparations. It did not, however, affect the increase in vascular smooth muscle cGMP or the dilatation induced by atrial natriuretic factor. ODQ had no effect on NO synthase activity, nor did it react with NO. It did, however, potently (IC50 approximately 10 nM) inhibit the activity of the SGC in cytosol obtained from crude extract of rat aortic smooth muscle. Thus ODQ prevents the actions of NO on platelets and vascular smooth muscle through its potent inhibitory effect on the SGC.
Analysis of the germination kinetics of individual Bacillus subtilis spores treated with hydrogen peroxide or sodium hypochlorite (2013)

This work shows that with Bacillus subtilis spore populations in which approximately 95% of individual spores were killed by several oxidizing agents, >95% of the spores in these populations germinated with nutrients, albeit slowly. This is important, as assay of an early germination event, release of dipicolinic acid, has been suggested as a rapid assay for spore viability and would give false-positive readings for the level of the killing of oxidizing agent-treated spore populations. Analysis of the germination kinetics of multiple individual untreated or oxidizing agent-treated spores also provides new information on proteins damaged by oxidizing agent treatment, and at least some of which are in spores' inner membrane.
Catecholamine innervation of the basal forebrain IV. Topography of the dopamine projection to the basal forebrain and neostriatum (1978)

In this study the location of dopamine (DA) neuron perikarya in the rostral mesencephalon of the rat was determined using the glyoxylic acid fluorescence histochemical technique. Subsequently the topography of the projection of these mesencephalic neurons on the basal forebrain and striatum was analyzed using the anterograde transport-autoradiographic tracing method and the retrograde transport-horseradish peroxidase (HRP) technique. The results of these anatomical studies were correlated with the biochemical and histochemical studies presented in previous reports (Moore, '78; Fallon and Moore, '78; Fallon et al., '78) to provide the following conclusions. The topography of the DA neuron projection of the basal forebrain and neostriatum is organized in three planes, dorsal-ventral, medial-lateral and anterior-posterior. DA cells are found almost exclusively in the substantia nigra (SN) and ventral tegmental area (VTA). Ventral cells of the SN and VTA project to the dorsal structures of the basal forebrain such as the septum, nucleus accumbens and neostriatum. The latter includes some DA cells located ventrally in the pars reticulata of the SN. Dorsal cells project to ventral structures. The medial-lateral topography is organized such that the medial sectors of the SN-VTA area project to the medial parts of nuclei in the basal forebrain and neostriatum whereas lateral sectors of the SN-VTA area project to the lateral parts of nuclei in the basal forebrain and neostriatum. An anterior-posterior topography also is evident such that anterior parts of the SN-VTA project anteriorly whereas the posterior SN-VTA projects more posteriorly in these areas. These observations are consistent with the view that the DA neurons of the SN-VTA complex form a single nuclear group with a highly topographically organized projection innervating not only deep nuclei of the telencephalon but allocortical structures as well.
Dipicolinic Acid Derivatives as Inhibitors of New Delhi Metallo-β-lactamase-1 (2017)

The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase (MBL) mediated resistance, specifically New Delhi metallo-β-lactamase-1 (NDM-1). By utilization of fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. On the basis of 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure-activity relationship (SAR) analysis. Inhibitor 36 (IC<sub>50</sub> = 80 nM) was identified to be highly selective for MBLs when compared to other Zn(II) metalloenzymes. While DPA displayed a propensity to chelate metal ions from NDM-1, 36 formed a stable NDM-1:Zn(II):inhibitor ternary complex, as demonstrated by <sup>1</sup>H NMR, electron paramagnetic resonance (EPR) spectroscopy, equilibrium dialysis, intrinsic tryptophan fluorescence emission, and UV-vis spectroscopy. When coadministered with 36 (at concentrations nontoxic to mammalian cells), the minimum inhibitory concentrations (MICs) of imipenem against clinical isolates of Eschericia coli and Klebsiella pneumoniae harboring NDM-1 were reduced to susceptible levels.
Photo-induced dissociation of electrospray generated ions in an ion trap/time-of-flight mass spectrometer (1999)

Laser photo-induced dissociation (PID) is an attractive alternative to collision-induced dissociation (CID) in probing structural features of biomolecules, such as peptides, by mass spectrometry. We report a new experimental setup for PID studies of biomolecules. It involves the use of an ion trap/time-of-flight mass spectrometer for the detection of PID products. The intact molecular ions are produced by electrospray ionization and introduced into a quadrupole ion trap. The ions stored in the trap are then dissociated by using a 266 nm laser beam from a pulsed Nd:yttrium–aluminium–garnet laser. After a short delay, all the fragment ions are extracted out of the trap and mass analyzed by a linear time-of-flight (TOF) mass spectrometer. The applications of this instrument for the PID studies of several peptides are demonstrated. The PID spectra are compared to those obtained by CID in the same instrument. It is shown that the amount of photoenergy deposited for fragmentation can be controlled by laser absorption property of the ions, laser power, number of laser pulses, and ion trap buffer gas pressure. Energetically optimal PID process results in spectra providing structural information similar to that obtained from CID. An excessive amount of photoenergy deposited to the fragmenting ions favors the formation of deep fragmentation products at the cost of sequence related ions. It is demonstrated that in some cases the PID technique has the potential in probing structural features of peptides that cannot be fragmented in ion trap CID. Finally, it is shown that the combination of the ion trap with the TOF detector provides a unique capability for fast detection of ions formed via PID. The PID products generated after a time delay from 1.5 μs to several milliseconds following the dissociation laser pulse can be characterized.
Diminished glucose transport and phosphorylation in Alzheimer's disease determined by dynamic FDG-PET. (1996)

These data suggest that hypometabolism in Alzheimer's disease is related to reduced glucose phosphorylation activity as well as diminished glucose transport, particularly in the most metabolically affected areas of the brain, the parietal and temporal cortex.
Monolithic integration via a universal damage enhanced quantum-well intermixing technique (1998)

A novel technique for quantum-well intermixing is demonstrated, which has proven a reliable means for obtaining postgrowth shifts in the band edge of a wide range of III-V material systems. The technique relies upon the generation of point defects via plasma induced damage during the deposition of sputtered SiO/sub 2/, and provides a simple and reliable process for the fabrication of both wavelength tuned lasers and monolithically integrated devices. Wavelength tuned broad area oxide stripe lasers are demonstrated in InGaAs-InAlGaAs, InGaAs-InGaAsP, and GaInP-AlGaInP quantum well systems, and it is shown that low absorption losses are obtained after intermixing. Oxide stripe lasers with integrated slab waveguides have also enabled the production of a narrow single lobed far field (3/spl deg/) pattern in both InGaAs-InAlGaAs, and GaInP-AlGaInP devices. Extended cavity ridge waveguide lasers operating at 1.5 /spl mu/m are demonstrated with low loss (/spl alpha/=4.1 cm/sup -1/) waveguides, and it is shown that this loss is limited only by free carrier absorption in waveguide cladding layers. In addition, the operation of intermixed multimode interference couplers is demonstrated, where four GaAs-AlGaAs laser amplifiers are monolithically integrated to produce high output powers of 180 mW in a single fundamental mode. The results illustrate that the technique can routinely be used to fabricate low-loss optical interconnects and offers a very promising route toward photonic integration.
Complete nucleotide sequences of Nipah virus isolates from Malaysia (2001)

We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.