gebhart/patrepeval huggingface dataset:
<title>Improved photosensitizers for photodynamic therapy</title> (1992)

In order to evaluate the effect of substituents in photosensitizing activity, a series of long wavelength absorbing photosensitizers related to pyropheophorbides, bacteriopheophorbides, and benzoporphyrin derivatives were synthesized. Pheophorbide dimers, covalently joining two molecules of pyropheophorbide-a and bacteriopheophorbide-a with lysine as a cross-link were also prepared. The syntheses and spectroscopic properties of these compounds are discussed. Some of these compounds were tested for in vivo photosensitizing activity vis-a-vis Photofrin II<SUP>TM</SUP>, using the standard screening system of DBA/2 mice bearing transplanted SMT/F tumors. The preliminary in vivo results suggest that replacement of substituents at peripheral positions of the macrocycles causes a significant difference in photosensitizing efficacy.
DeskBench: Flexible virtual desktop benchmarking toolkit (2009)

The thin-client computing model has been recently regaining popularity in a new form known as the virtual desktop. That is where the desktop is hosted on a virtualized platform. Even though the interest in this computing paradigm is broad there are relatively few tools and methods for benchmarking virtual client infrastructures. We believe that developing such tools and approaches is crucial for the future success of virtual client deployments and also for objective evaluation of existing and new algorithms, communication protocols, and technologies. We present DeskBench, a virtual desktop benchmarking tool, that allows for fast and easy creation of benchmarks by simple recording of the user's activity. It also allows for replaying the recorded actions in a synchronized manner at maximum possible speeds without compromising the correctness of the replay. The proposed approach relies only on the basic primitives of mouse and keyboard events as well as screen region updates which are common in window manager systems. We have implemented a prototype of the system and also conducted a series of experiments measuring responsiveness of virtual machine based desktops under various load conditions and network latencies. The experiments illustrate the flexibility and accuracy of the proposed method and also give some interesting insights into the scalability of virtual machine based desktops.
N-Terminus of IpaB Provides a Potential Anchor to the <i>Shigella</i> Type III Secretion System Tip Complex Protein IpaD (2013)

The type III secretion system (T3SS) is an essential virulence factor for Shigella flexneri , providing a conduit through which host-altering effectors are injected directly into a host cell to promote uptake. The type III secretion apparatus (T3SA) is composed of a basal body, external needle, and regulatory tip complex. The nascent needle is a polymer of MxiH capped by a pentamer of invasion plasmid antigen D (IpaD). Exposure to bile salts (e.g., deoxycholate) causes a conformational change in IpaD and promotes recruitment of IpaB to the needle tip. It has been proposed that IpaB senses contact with host cell membranes, recruiting IpaC and inducing full secretion of T3SS effectors. Although the steps of T3SA maturation and their external triggers have been identified, details of specific protein interactions and mechanisms have remained difficult to study because of the hydrophobic nature of the IpaB and IpaC translocator proteins. Here, we explored the ability for a series of soluble N-terminal IpaB peptides to interact with IpaD. We found that DOC is required for the interaction and that a region of IpaB between residues 11-27 is required for maximum binding, which was confirmed in vivo. Furthermore, intramolecular FRET measurements indicated that movement of the IpaD distal domain away from the protein core accompanied the binding of IpaB11-226. Together, these new findings provide important new insight into the interactions and potential mechanisms that define the maturation of the Shigella T3SA needle tip complex and provide a foundation for further studies probing T3SS activation.
Targeted Fc2′-3-PE40 chimeric protein abolishes passive cutaneous anaphylaxis in mice (2000)

The alarming increase in the incidence of allergic diseases in the past decade has led to a clear call for more effective treatment. Recently, we reported on the construction of a chimeric protein for targeted elimination of cells expressing FcepsilonRI receptors. This chimeric protein, designated Fc2'-3-PE40, is composed of a Fc fragment of mouse IgE attached to a truncated form of Pseudomonas exotoxin. The Fc2'-3-PE40 chimeric protein was found to be highly cytotoxic to mouse mast cell lines and primary mouse mast cells. We now demonstrate that Fc2'-3-PE40 successfully prevents the development of passive cutaneous anaphylaxis reaction (PCA) in mice. Treatment with Fc2'-3-PE40 for 7 days prevented the PCA reaction in mice by 80% compared with that in control mice given only PBS. Fc2'-3-PE40M, the mutated, enzymatically inactive analogue of Fc2'-3-PE40, did not display this activity. Fc2'-3-PE40 was also effective when given as a single dose 16 h before antigen exposure, resulting in complete inhibition of the PCA reaction. Moreover, treatment with Fc2'-3-PE40 did not cause mast cell degranulation, as the serum histamine values of mice treated with Fc2'-3-PE40 were within the range obtained for control, untreated mice. Thus, the Fc2'-3-PE40 chimeric protein offers a novel approach to the treatment of allergic disorders.
Channel identification machines for multidimensional receptive fields (2014)

We present algorithms for identifying multidimensional receptive fields directly from spike trains produced by biophysically-grounded neuron models. We demonstrate that only the projection of a receptive field onto the input stimulus space may be perfectly identified and derive conditions under which this identification is possible. We also provide detailed examples of identification of neural circuits incorporating spatiotemporal and spectrotemporal receptive fields.
Single-mode ARROW-type diode lasers (1993)

Design, fabrication, and characteristics of Antiresonant Reflecting Optical Waveguide (ARROW)-type diode lasers are presented. A complete two-dimensional optical waveguide analysis of the self-aligned-stripe (sas) ARROW-type laser indicates strong single-mode selectivity in these structures. Large core-width devices (10 micron) are expected to operate in a stable, single lateral mode, permitting the potential for reliable single-mode operation in the several hundred milliwatt range.
Total Synthesis of [Ψ[C(═NH)NH]Tpg<sup>4</sup>]Vancomycin and its (4-Chlorobiphenyl)methyl Derivative: Impact of Peripheral Modifications on Vancomycin Analogues Redesigned for Dual <scp>d</scp>-Ala-<scp>d</scp>-Ala and <scp>d</scp>-Ala-<scp>d</scp>-Lac Binding (2014)

The total synthesis of two key analogues of vancomycin containing single-atom exchanges in the binding pocket (residue 4 amidine and thioamide) are disclosed as well as their peripherally modified (4-chlorobiphenyl)methyl (CBP) derivatives. Their assessment indicates that combined pocket amidine and CBP peripherally modified analogues exhibit a remarkable spectrum of antimicrobial activity (VSSA, MRSA, VanA and VanB VRE) and impressive potencies (MIC = 0.06-0.005 μg/mL) against both vancomycin-sensitive and -resistant bacteria and likely benefit from two independent and synergistic mechanisms of action. Like vancomycin, such analogues are likely to display especially durable antibiotic activity not prone to rapidly acquired clinical resistance.
Photopumped low threshold Al<i>x</i>″Ga1−<i>x</i>″As -Al<i>x</i>′Ga1−<i>x</i>′As-Al<i>x</i>Ga1−<i>x</i>As (<i>x</i>″∼0.85, <i>x</i>′∼0.3, <i>x</i>=0) single quantum well lasers (1983)

Data are presented showing that it is possible to photopump and operate a quantum well heterostructure laser at equivalent current densities (Jeq) as low as 70 A/cm2. Continuous 300-K laser operation of a single 60-Å GaAs (x=0) quantum well in the center of a ∼0.12-μm-thick x′∼0.30 Alx′Ga1−x′As waveguide (and carrier reservoir), which is confined by x″∼0.85 Alx″Ga1−x″As layers, is demonstrated at Ieq∼0.4 mA (168 W/cm2, Jeq∼70 A/cm2). These quantum well heterostructures are grown by organometallic vapor phase epitaxy.
Human sulfotransferase SULT1C1 pharmacogenetics: gene resequencing and functional genomic studies (2001)

Sulfotransferase (SULT) enzymes catalyze an important phase II reaction in the biotransformation of many drugs and other xenobiotics. We previously cloned the human SULT1C1 cDNA and gene as steps toward pharmacogenetic studies. We have now 'resequenced' the exons, portions of introns flanking exons and approximately 315 bp of the 5' flanking region of SULT1C1 in 89 DNA samples from Caucasian subjects to identify common genetic polymorphisms. Nineteen separate polymorphisms were observed, including four nonsynonymous coding region single nucleotide polymorphisms (cSNPs) and five insertions/deletions. These data were also used to determine and/or infer common SULT1C1 haplotypes. Three of the four nonsynonymous cSNPs had allele frequencies greater than 1%, including one with a frequency of 6.7%. Expression constructs were created for all of the nonsynonymous cSNPs observed, and those constructs were used to transfect COS-1 cells. Three of the four SULT1C1 variant allozymes had significantly reduced enzyme activity when compared with the wild-type enzyme. Among the variant allozymes, apparent Km values for 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the sulfate donor for the reaction, varied 7-fold, and quantitative Western blot analysis showed variable levels of immunoreactive protein when compared to the wild-type enzyme. Therefore, mechanisms responsible for decreased activity involved both alterations in levels of enzyme protein and alterations in substrate kinetics. In summary, application of a 'genotype to phenotype' strategy has resulted in the identification of a series of functionally significant common genetic polymorphisms for SULT1C1. It will now be possible to evaluate the possible contribution of these polymorphisms to variation in the sulfate conjugation of drugs, other xenobiotics and/or disease pathophysiology.
Ecotin is a potent inhibitor of the contact system proteases factor XIIa and plasma kallikrein (1995)

Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, has been characterized as a potent reversible tight-binding inhibitor of the human contact activation proteases factor XIIa (FXIIa) and plasma kallikrein, having Ki values of 89 pM and 163 pM, respectively. Ecotin also inhibited human leukocyte elastase (HLE) with high affinity (Ki = 55 pM). The association rate constants kon for FXIIa and kallikrein were 5.3 x 10(5) M-1.s-1 and 2.9 x 10(5) M-1.s-1, respectively. The dissociation rate constant koff for kallikrein, measured in the presence of HLE to prevent reassociation, was 6.3 x 10(-5) s-1; the koff for ecotin with FXIIa was 4.7 x 10(-5) s-1. Both FXIIa and kallikrein cleaved ecotin slowly at pH 5.0, identifying Met-84 as the P1 residue. The potent anticoagulant effect by ecotin is explained by the coincident inhibition of FXIIa, kallikrein, and FXa and suggests that it may be useful in the study of inflammatory or thrombotic disorders such as sepsis or cardiopulmonary bypass.
Template Synthesis of Iron(II) Complexes Containing Tridentate P−N−S, P−N−P, P−N−N, and Tetradentate P−N−N−P Ligands (2009)

A series of mer-tridentate iron(II) complexes bearing P-N-S (3), P-N-P (4), and P-N-N (5) ligands have been prepared via the metal template effect in one pot involving air-stable phosphonium dimers [cyclo-(-PPh(2)CH(2)C(OH)H-)(2)](Br)(2) (1) and [cyclo-(-PCy(2)CH(2)C(OH)H-)(2)](Br)(2) (2), KOtBu, [Fe(H(2)O)(6)][BF(4)](2) and 2-aminothiolphenol (for 3), 2-(diphenylphosphino)ethylamine (for 4), and 2-(aminomethyl)pyridine (for 5). The new phosphonium dimer 2 was prepared via an S(N)2 reaction of PCy(2)H with BrCH(2)CH(OEt)(2). The complexes Fe{PR(2)CH(2)CH=N(2-C(6)H(4))S}(2)FeBr(2) (3a, R = Ph; 3b, R = Cy) are paramagnetic, and X-ray diffraction studies revealed that they are bimetallic, in which the S atoms of the bis-tridentate (PNS)(2)Fe unit bridge to a FeBr(2) fragment. Complexes [Fe(PR(2)CH(2)CH=NC(2)H(4)PPh(2))(NCMe)(3)]X(2) (4a, R = Ph; 4b, R = Cy; X(2) = FeBr(4) or (BF(4))(2)) form when 1 equiv of iron is reacted with PPh(2)CH(2)CH(2)NH(2) and 0.5 equiv of the appropriate phosphonium dimer. The evidence for P-N-P coordination is the large (2)J(PP) coupling constant in the (31)P {(1)H} NMR spectrum for the trans phosphorus nuclei. If 0.5 equiv of [Fe(H(2)O)(6)][BF(4)](2) were added in the synthesis, the complex trans-[Fe(NCMe)(2)(Ph(2)PC(2)H(4)NH(2))(2)][FeBr(4)] (4c) formed, and this has been characterized by X-ray diffraction. Complexes [Fe{PR(2)CH(2)CH=NCH(2)(2-C(5)H(4)N)}(2)](BPh(4))(2) (5) are bis-tridentate iron(II) complexes with pyridyl donors trans to the phosphine donors. Interestingly, addition of the diamines ethylenediamine, (1R,2R)-(-)-1,2-diaminocyclohexane, (1R,2R)-(-)-1,2-diphenylethylenediamine, or o-phenylenediamine, in the template synthesis with 2 led directly to tetradentate P-N-N-P iron(II) complexes trans-[Fe(NCMe)(2)(PCy(2)CH(2)CH=N-Q-N=CHCH(2)PCy(2)](BPh(4))(2) (Q = CH(2)CH(2), 6a; Q = (1R,2R)-cyclo-C(6)H(10), 6b; Q = (1R,2R)-CHPhCHPh, 6c; Q = C(6)H(4), 6d). In contrast, similar reactions under the same conditions with dimer 1 led to complexes mer-[Fe(P-N-N)(2)](2+) as reported previously. Complexes 6a and 6b have been characterized by X-ray diffraction and exhibited large P-Fe-P bond angles of 112.92(2) and 111.96(4) degrees, respectively.
Branched Polymeric Media: Perchlorate-Selective Resins from Hyperbranched Polyethyleneimine (2012)

Perchlorate (ClO(4)(-)) is a persistent contaminant found in drinking groundwater sources in the United States. Ion exchange (IX) with selective and disposable resins based on cross-linked styrene divinylbenzene (STY-DVB) beads is currently the most commonly utilized process for removing low concentrations of ClO(4)(-) (10-100 ppb) from contaminated drinking water sources. However, due to the low exchange capacity of perchlorate-selective STY-DVB resins (∼0.5-0.8 eq/L), the overall cost becomes prohibitive when treating groundwater with higher concentration of ClO(4)(-) (e.g., 100-1000 ppb). In this article, we describe a new perchlorate-selective resin with high exchange capacity. This new resin was prepared by alkylation of branched polyethyleneimine (PEI) beads obtained from an inverse suspension polymerization process. Batch and column studies show that our new PEI resin with mixed hexyl/ethyl quaternary ammonium chloride exchange sites can selectively extract trace amounts of ClO(4)(-) from a makeup groundwater (to below detection limit) in the presence of competing ions. In addition, this resin has a strong-base exchange capacity of 1.4 eq/L, which is 1.75-2.33 times larger than those of commercial perchlorate-selective STY-DVB resins. The overall results of our studies suggest that branched PEI beads provide versatile and promising building blocks for the preparation of perchlorate-selective resins with high exchange capacity.
Precise and Efficient Crispr/Cas9 Mediated Gene Editing in Long-Term Engrafting Human Hematopoietic Stem/Progenitor Cells (2016)

Abstract Transplantation of gene-modified autologous hematopoietic stem/progenitor cells (HSPCs) is an effective treatment for several hematologic diseases. However, a number of blood disorders may not be amenable to gene augmentation-based therapeutics. Targeted genome editing in human HSPCs could provide a therapeutic approach for these otherwise untreatable diseases. Here we demonstrate that CRISPR/Cas9 ribonucleoprotein (RNP) edits target genes in human HSPCs with high efficiency and precision. Human adult and umbilical cord blood (CB) CD34+ cells from 20 donors were electroporated with S. pyogenes or S. aureus Cas9 RNP targeting HBB, AAVS1, or CXCR4. Sequence analysis demonstrated up to 80% editing in CB CD34+ cells (mean±s.d: 61%±9%) and up to 57% in adult CD34+ cells (39%±13%). Delivery of Cas9 RNP and a single-stranded oligodeoxynucleotide donor (ssODN) led to up to 12% ssODN-mediated homology directed repair (HDR) and also led to a 20% increase in total gene editing (HDR+NHEJ)(RNP: 48%±15%; RNP+ssODN: 69%±8%). Both Cas9 RNP gene-edited CD34+ cells and donor-matched untreated control CD34+ cells reconstituted human hematopoiesis in primary and secondary recipient immunodeficient mice, with ~85% human CD45+ cell peripheral blood reconstitution 4 months after primary transplantation. Human T and B lymphoid, erythroid, and myeloid cells were detected in the spleen, thymus, and bone marrow with 20% CD34+ cell engraftment in the marrow of mice transplanted with RNP gene-edited or control CD34+ cells. The level of targeted gene editing in human erythroid, myeloid, and CD34+ cells that were recovered and enriched from the hematopoietic organs of primary recipients (~50%) was similar to the level of gene editing detected in the pre-infusion product (~60%). In summary, these results indicate that Cas9 gene-edited human HSPCs retain long-term engraftment potential and support multilineage blood reconstitution in vivo, thus supporting further investigation of CRISPR/Cas9 mediated gene-edited hematopoietic stem/progenitor cell therapies. Disclosures Heath: Editas Medicine: Employment. Chalishazar:Editas Medicine: Employment. Lee:Editas Medicine: Employment. Selleck:Editas Medicine: Employment. Cotta-Ramusino:Editas Medicine: Employment. Bumcrot:Editas Medicine: Employment. Gori:Editas Medicine: Employment.
Effect of fly ash on the sulfate resistance of concrete containing fly ash (1988)

The durability of concrete is determined by its ability to endure the physical and environmental surroundings without losing the functional properties and structural integrity of the original design. Concrete containing fly ash can be proportioned to meet the durability requirements of a wide range of applications, such as concrete for mass structure, pavements, structural members, and high strength applications. One area where the long term performance of concrete containing high calcium fly ash has been suspect is in sulfate environments. The sulfate attack mechanism in concrete containing fly ash has been related in recent years to the mineralogical and chemical characteristics of portland cement and fly ash and their proportions, and the sulfate resistance of concrete containing fly ash. This report summarizes the results of the first year of the study. Fourteen fly ashes and four portland cements have been studied at four cement replacement levels and two different workability levels. A wet chemistry analysis was performed to determine the bulk chemical properties of both the fly ashes and the portland cements. The mineralogy of the fly ash was determined by XRD analysis. Over 500 concrete specimens have been exposure tested in a 10 per cent sodium sulfate solution and monitored for mass change and linear expansion. The study has revealed a possible correlation between the tricalcium aluminate content of the high calcium fly ash and sulfate deterioration. In addition, the results to date indicate that lignitic fly ashes result in sulfate resistant concrete. This is an interim report of an ongoing investigation to the problem of sulfate attack of concrete containing fly ash (A).
Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility (2010)

Throughout the battery of experiments, the compounds kb-NB142-70 and kb-NB165-09 emerged as the most potent and specific analogs in vitro and in cells. These compounds are undergoing further testing for their effectiveness as pharmacological tools for dissecting PKD function and as potential anti-cancer agents in the treatment of prostate cancer.
Intrinsic aberrations due to Mie scattering in particle holography (2003)

Holography of small particles is a newly revived topic because of its importance in holographic particle image velocimetry (HPIV). However, the property of particle images formed through holography remains largely unexplored. This fact undermines the measurement reliability of HPIV techniques and has become one of the obstacles in the full deployment of HPIV. We study the intrinsic aberrations in the holographic particle image introduced by particle light scattering and investigate how accurately holography can deliver information about the particles that are being imaged. Consistent with our experimental observations, simulations based on Mie scattering theory show that even with a perfect hologram the reconstructed particle images demonstrate complex three-dimensional morphologies and bodily shifts. These characteristics, manifested as image aberrations, result from uneven scattering amplitude and phase distributions across the finite aperture of the hologram. Such aberrations degrade the signal-to-noise ratio in the reconstructed image as well as introducing systematic errors in detected particle image positions. We examine the effect of these aberrations on HPIV measurements.
Formation of Hydroxyapatite in Cement Systems: Effects of Phosphate (1999)

The rate of hydroxyapatite (HA) formation in several calcium phosphate cement (CPC) systems was promoted when a phosphate solution instead of water was used as the cement liquid. The accelerated HA formation reduced the hardening time (HT) of the cements. In the cement system consisting of tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous (DCPA), and distilled water, the presence of small TTCP particles (median diameter of 2.7 μm) reduced phosphate concentration in liquid phase, inhibited HA formation, and prolonged HT.
The Complete Gene Cluster of the Antitumor Agent Gilvocarcin V and Its Implication for the Biosynthesis of the Gilvocarcins (2003)

Gilvocarcin V, an antitumor agent produced by the bacterium Streptomyces griseoflavus Gö 3592, is the most studied representative of the distinct family of benzo[d]naphtho[1,2-b]pyran-6-one aryl C-glycoside antibiotics, which show excellent antitumor activity and a remarkably low toxicity. Its biosynthesis contains many intriguing steps, including an oxidative rearrangement, the C-glycosylation, and the generation of a vinyl side chain. These steps all contribute to structural elements of the drug, which are essential for its biological activity, but only poorly understood. Herein we report the cloning and characterization of the gilvocarcin (gil) gene cluster from S. griseoflavus Gö 3592, and its heterologous expression in a foreign host (S. lividans). This is the first reported gene cluster encoding the biosynthesis of a benzo[d]naphtho[1,2-b]pyran-6-one aryl C-glycoside antibiotic, which not only provides insights regarding the biosynthesis of gilvocarcin V but also lays the foundation for the detailed studies of its intriguing biosynthetic steps and possibly for the generation of gilvocarcin analogues with improved biological activities through combinatorial biosynthesis.
Wave-front shaping for nonlinear light propagation in multimode fibers (2017)

We demonstrate a wave-front-shaping approach for controlling nonlinear phenomena in multimode fibers. Using a spatial light modulator at the fiber’s input and optimization algorithms, we control highly nonlinear propagation targeting selected wavelengths and interactions.