gebhart/patrepeval huggingface dataset:
2-D wavelength demultiplexer with potential for > or = to 1000 channels in the C-band (2004)

We demonstrate a 2-D wavelength demultiplexer by using a (3)virtually imaged phased array (VIPA) and a diffraction grating in bulk optics, which yields a hyperfine channel spacing 5 GHz (40 pm) with 1.75 GHz (14 pm) -3dB bandwidth, >20dB channel isolations, and a very large free spectral range. The 2-D wavelength demultiplexer is capable of having a very large number ((3)1000) of hyperfine channels in the C-band (1530 - 1570 nm). We also present the first analytic theory for the 2-D demultiplexer.
Unique physiology of host-parasite interactions in microsporidia infections (2009)

Microsporidia are intracellular parasites of all major animal lineages and have a described diversity of over 1200 species and an actual diversity that is estimated to be much higher. They are important pathogens of mammals, and are now one of the most common infections among immunocompromised humans. Although related to fungi, microsporidia are atypical in genomic biology, cell structure and infection mechanism. Host cell infection involves the rapid expulsion of a polar tube from a dormant spore to pierce the host cell membrane and allow the direct transfer of the spore contents into the host cell cytoplasm. This intimate relationship between parasite and host is unique. It allows the microsporidia to be highly exploitative of the host cell environment and cause such diverse effects as the induction of hypertrophied cells to harbour prolific spore development, host sex ratio distortion and host cell organelle and microtubule reorganization. Genome sequencing has revealed that microsporidia have achieved this high level of parasite sophistication with radically reduced proteomes and with many typical eukaryotic pathways pared-down to what appear to be minimal functional units. These traits make microsporidia intriguing model systems for understanding the extremes of reductive parasite evolution and host cell manipulation.
Immunization with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and effect of revaccination (1988)

Previously we showed that mice immunized with a vaccinia virus vector expressing the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) gene (vaccinia/gD) were protected against both lethal and latent infections with HSV-1 for at least 6 weeks after immunization (K. J. Cremer, M. Mackett, C. Wohlenberg, A. L. Notkins, and B. Moss, Science 228:737-740, 1985). In the experiments described here, we examined long-term immunity to HSV following vaccinia/gD vaccination, the effect of revaccination with vaccinia/gD, and the impact of previous immunity to vaccinia virus on immunization with the gD recombinant. Mice immunized with vaccinia/gD showed 100, 100, and 80% protection against lethal infection with HSV-1 at 18, 44, and 60 weeks postimmunization, respectively. Protection against latent trigeminal ganglionic infection was 70, 50, and 31% at 6, 41, and 60 weeks postvaccination, respectively. To study the effect of reimmunization on antibody levels, mice vaccinated with vaccinia/gD were given a second immunization (booster dose) 3 months after the first. These mice developed a 10-fold increase in neutralizing-antibody titer (221 to 2,934) and demonstrated a significant increase in protection against lethal HSV-1 challenge compared with animals that received only one dose of vaccinia/gD. To determine whether preexisting immunity to vaccinia virus inhibited the response to vaccination with vaccinia/gD virus, mice were immunized with a recombinant vaccinia virus vector expressing antigens from either influenza A or hepatitis B virus and were then immunized (2 to 3 months later) with vaccinia/gD. These mice showed reduced titers of neutralizing antibody to HSV-1 and decreased protection against both lethal and latent infections with HSV-1 compared with animals vaccinated only with vaccinia/gD. We conclude that vaccination with vaccinia/gD produces immunity against HSV-1 that lasts over 1 year and that this immunity can be increased by a booster but that prior immunization with a vaccinia recombinant virus expressing a non-HSV gene reduces the levels of neutralizing antibody and protective immunity against HSV-1 challenge.
Biocompatibility of microparticles into soft tissue fillers (2004)

The increasing need for long-lasting injectable soft tissue fillers for the treatment of wrinkles and folds requires a critical discussion of the biocompatibility on a scientific background. Since biological fillers made of collagen and hyaluronic acid will be resorbed over time, copolymer biomaterials with microparticles have been developed in recent years. The microparticles followed special and essential demands because of the interaction with the tissue. In search of an ideal soft tissue filler substance, a variety of biomaterials with microparticles suspended have been created for injecting into dermal defects, into the urethra of patients with urinary incontinence, and in patients with vocal cord insufficiency. The particles differ in chemical composition, surface structure, surface charge, and particle size and evoke different host reactions, accordingly.
Current issues relating to the transfusion of stored red blood cells (2008)

The development of blood storage systems allowed donation and transfusion to be separated in time and space. This separation has permitted the regionalization of donor services with subsequent economies of scale and improvements in the quality and availability of blood products. However, the availability of storage raises the question of how long blood products can and should be stored and how long they are safe and effective. The efficacy of red blood cells was originally measured as the increment in haematocrit and safety began with typing and the effort to reduce the risk of bacterial contamination. Appreciation of a growing list of storage lesions of red blood cells has developed with our increasing understanding of red blood cell physiology and our experience with red blood cell transfusion. However, other than frank haemolysis, rare episodes of bacterial contamination and overgrowth, the reduction of oxygen-carrying capacity associated with the failure of some transfused cells to circulate, and the toxicity of lysophospholipids released from membrane breakdown, storage-induced lesions have not had obvious correlations with safety or efficacy. The safety of red blood cell storage has also been approached in retrospective epidemiologic studies of transfused patients, but the results are frequently biased by the fact that sicker patients are transfused more often and blood banks do not issue blood products in a random order. Several large prospective studies of the safety of stored red blood cells are planned.
Episomal Vectors Rapidly and Stably Produce High-Titer Recombinant Retrovirus (1996)

The nuclear replication and retention functions of the Epstein-Barr virus (EBV) have been utilized here to maintain retroviral constructs episomally within human cell-based retroviral packaging lines. These hybrid EBV/retroviral constructs are capable of producing helper-free recombinant retrovirus as soon as 48 hr and for at least 30 days after transfection into 293T-based ecotropic and/or amphotropic retroviral packaging cells. Viral titers greater than 10(7) TU/ml were obtained after puromycin selection of transfected retroviral packaging cells. This episomal approach to retroviral production circumvents some limitations inherent in transient and chromosomally stable retroviral producer systems, affording reproducibly rapid, large-scale, stable, and high-titer retrovirus production.
Roles of Gβγ in membrane recruitment and activation of p110γ/p101 phosphoinositide 3-kinase γ (2002)

Receptor-regulated class I phosphoinositide 3-kinases (PI3K) phosphorylate the membrane lipid phosphatidylinositol (PtdIns)-4,5-P2 to PtdIns-3,4,5-P3. This, in turn, recruits and activates cytosolic effectors with PtdIns-3,4,5-P3-binding pleckstrin homology (PH) domains, thereby controlling important cellular functions such as proliferation, survival, or chemotaxis. The class IB p110 gamma/p101 PI3K gamma is activated by G beta gamma on stimulation of G protein-coupled receptors. It is currently unknown whether in living cells G beta gamma acts as a membrane anchor or an allosteric activator of PI3K gamma, and which role its noncatalytic p101 subunit plays in its activation by G beta gamma. Using GFP-tagged PI3K gamma subunits expressed in HEK cells, we show that G beta gamma recruits the enzyme from the cytosol to the membrane by interaction with its p101 subunit. Accordingly, p101 was found to be required for G protein-mediated activation of PI3K gamma in living cells, as assessed by use of GFP-tagged PtdIns-3,4,5-P3-binding PH domains. Furthermore, membrane-targeted p110 gamma displayed basal enzymatic activity, but was further stimulated by G beta gamma, even in the absence of p101. Therefore, we conclude that in vivo, G beta gamma activates PI3K gamma by a mechanism assigning specific roles for both PI3K gamma subunits, i.e., membrane recruitment is mediated via the noncatalytic p101 subunit, and direct stimulation of G beta gamma with p110 gamma contributes to activation of PI3K gamma.
Synthesis and in Vitro Antiprotozoal Activities of Water-Soluble, Inexpensive 3,7-Bis(dialkylamino)phenoxazin-5-ium Derivatives (2008)

3,7-Bis(dialkylamino)phenoxazinium salts were synthesized and evaluated for in vitro activities against Plasmodium falciparum, Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania donovani. Notably, the compounds showed potent antiprotozoal activities, especially against P. falciparum and T. cruzi. The compounds with alkyl side chains less than three carbons in length possessed good activities with high selective indices.
Oxide Contacts in Organic Photovoltaics: Characterization and Control of Near-Surface Composition in Indium−Tin Oxide (ITO) Electrodes (2009)

The recent improvements in the power conversion efficiencies of organic photovoltaic devices (OPVs) promise to make these technologies increasingly attractive alternatives to more established photovoltaic technologies. OPVs typically consist of photoactive layers 20-100 nm thick sandwiched between both transparent oxide and metallic electrical contacts. Ideal OPVs rely on ohmic top and bottom contacts to harvest photogenerated charges without compromising the power conversion efficiency of the OPV. Unfortunately, the electrical contact materials (metals and metal oxides) and the active organic layers in OPVs are often incompatible and may be poorly optimized for harvesting photogenerated charges. Therefore, further optimization of the chemical and physical stabilities of these metal oxide materials with organic materials will be an essential component of the development of OPV technologies. The energetic and kinetic barriers to charge injection/collection must be minimized to maximize OPV power conversion efficiencies. In this Account, we review recent studies of one of the most common transparent conducting oxides (TCOs), indium-tin oxide (ITO), which is the transparent bottom contact in many OPV technologies. These studies of the surface chemistry and surface modification of ITO are also applicable to other TCO materials. Clean, freshly deposited ITO is intrinsically reactive toward H(2)O, CO, CO(2), etc. and is often chemically and electrically heterogeneous in the near-surface region. Conductive-tip atomic force microscopy (C-AFM) studies reveal significant spatial variability in electrical properties. We describe the use of acid activation, small-molecule chemisorption, and electrodeposition of conducting polymer films to tune the surface free energy, the effective work function, and electrochemical reactivity of ITO surfaces. Certain electrodeposited poly(thiophenes) show their own photovoltaic activity or can be used as electronically tunable substrates for other photoactive layers. For certain photoactive donor layers (phthalocyanines), we have used the polarity of the oxide surface to accelerate dewetting and "nanotexturing" of the donor layer to enhance OPV performance. These complex surface chemistries will make oxide/organic interfaces one of the key focal points for research in new OPV technologies.
Site-directed mutagenesis of glutathione S-transferase YaYa. Mapping the glutathione-binding site. (1993)

Previous studies from our laboratory have shown that aspartic acid 101 plays an important role in glutathione interaction to rat glutathione S-transferase YaYa, while tyrosine 9 is directly involved in catalysis. Based on the available structural information, site-directed mutagenesis was conducted to examine the function of arginine, lysine, glutamine, and proline residues surrounding the GSH binding pocket. Arginine mutants R13K, R15K, R20K, and R20I retained partial enzymatic activities, while R13I and R15I lost most of their activities. Kinetic studies showed a marked increase in Km toward GSH for R15I suggesting that arginine 15 contributes significantly to the binding of GSH in the active site of glutathione S-transferase YaYa. A drastic decrease in enzymatic activities for R13I suggested the importance of the charged group of arginine 13 either in maintaining the structural integrity of the enzyme or in serving a vital role in enzymatic function. Replacement of glutamine 54 and 67 with glutamic acid or asparagine resulted in decreased enzymatic activities. Moreover, an 11-, 17-, and 9-fold increase in Km values toward GSH for mutant Q54E, Q54N, and Q67N was observed, respectively. These results suggested that glutamine 54 and 67 also contributed significantly to the binding of GSH. Proline at position 56 appears to be important for maintaining the structural integrity of the enzyme since mutants P56A and P56F were much less active and extremely less stable than that of the wild type enzyme. Both lysine mutants, K45R and K45I, exhibited substantially higher catalytic efficiencies toward both 1-chloro-2,4-dinitrobenzene and GSH than the wild type enzyme. Our data clearly show that lysine 45 is not an essential residue for catalysis nor for GSH binding in glutathione S-transferase YaYa.
Suppression of polymorphonuclear leukocyte chemotactic factor production in Propionibacterium acnes by subminimal inhibitory concentrations of tetracycline, ampicillin, minocycline, and erythromycin (1982)

Propionibacterium acnes is the cause of inflammation in acne vulgaris and has been shown to produce potent neutrophil chemoattractants. Different strain of P. acnes that were sensitive or resistant to ampicillin, erythromycin, minocycline, and tetracycline were grown in the presence of subminimal inhibitory concentrations of the drugs, and their culture supernatants were assayed for neutrophil chemotactic activity. The presence of subminimal inhibitory concentrations of ampicillin failed to affect chemotactic factor production by any of the strains. Subminimal inhibitory concentrations of tetracycline, minocycline, and erythromycin all produced decreased neutrophil chemotactic activity in P. acnes culture supernatants. This inhibition of chemotactic activity was most pronounced in strains of P. acnes which were susceptible to the drugs. The addition of antibiotics at appropriate concentrations to control supernatants failed to affect neutrophil migration. The results indicate that subminimal inhibitory concentrations of antibiotics are capable of reducing the inflammatory capacity of P. acnes.
Cells of the yeast Saccharomyces cerevisiae are transformable by DNA under non‐artificial conditions (2000)

Transformants of bakers' yeast (Saccharomyces cerevisiae) can be generated when non-growing cells metabolize sugars (without additional nutrients) in the presence of plasmid DNA. These results suggest that there is a mechanism by which DNA can naturally be taken up by the yeast cell. Natural transformation does not take place in common complete or minimal yeast culture media such as YPD and YNB. The starvation conditions used in our experiments thus seem to be an important prerequisite for such transformation events. Copyright © 2000 John Wiley & Sons, Ltd.
A first-in-human, phase I study of an oral hedgehog (HH) pathway antagonist, BMS-833923 (XL139), in subjects with advanced or metastatic solid tumors. (2010)

2501 Background: Aberrant HH pathway signaling has been suggested to play a role in the development of multiple solid tumors and hematological malignancies. BMS-833923 is a potent, oral, small molecule antagonist of the HH signaling component Smoothened. Methods: The trial is designed to identify a maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics. All subjects receive a single dose 1 week prior to continuous daily dosing, which allows for single dose PK collection for 1 week. To identify the pharmacologically active dose range, skin samples are collected prior to day 1 and again on day 22 of the first cycle to assess GLI1 protein expression levels. Results: As of October 21, 2009, eighteen subjects (mean age of 56 [range 21-78]; ECOG performance 0--1) have been treated at four dose levels: 30 mg (n=5), 60 mg (n=3), 120 mg (n=3), and 240 mg (n=7). No subjects in the first three dose cohorts experienced drug-related CTCAE adverse events greater than grade 2. One subject with medulloblastoma in the 30 mg dose cohort continues on study for >11 months with stable disease. Treatment of subjects in the fourth cohort at 240 mg is ongoing. In this cohort, a 50 year old female subject with Gorlin Syndrome, caused by germline mutation in the HH pathway gene Patched, experienced an ongoing confirmed partial response. This subject experienced drug-related CTCAE grade 2 lipase elevation and pancreatitis that quickly resolved when drug was withheld. The subject is currently receiving a single 60 mg dose every other week. BMS-833923 PK properties showed dose proportionality between the 30, 60, and 120 mg dose cohorts and greater than dose proportionality between the 120 mg and 240 mg dose cohorts. All dose cohorts show a prolonged terminal half-life of >7 days with drug accumulation of 3-6 fold between days 1 and 22 as measured by changes in the Cmax. Measurement of GLI1 protein expression in the skin biopsies shows a decrease at all dose levels. Conclusions: BMS-833923 is generally well tolerated at the dose levels tested, which include dose levels that are clinically active. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb, Merck, Millennium Bristol-Myers Squibb Bayer, Bristol-Myers Squibb, Cyclacel Pharmaceuticals, GlaxoSmithKline, Merck, Novartis, Pfizer, Regeneron, Roche Bristol-Myers Squibb Bristol-Myers Squibb
Molecular Similarity Indices in a Comparative Analysis (CoMSIA) of Drug Molecules to Correlate and Predict Their Biological Activity (1994)

An alternative approach is reported to compute property fields based on similarity indices of drug molecules that have been brought into a common alignment. The fields of different physicochemical properties use a Gaussian-type distance dependence, and no singularities occur at the atomic positions. Accordingly, no arbitrary definitions of cutoff limits and deficiencies due to different slopes of the fields are encountered. The fields are evaluated by a PLS analysis similar to the CoMFA formalism. Two data sets of steroids binding to the corticosteroid-binding-globulin and thermolysin inhibitors were analyzed in terms of the conventional CoMFA method (Lennard-Jones and Coulomb potential fields) and the new comparative molecular similarity indices analysis (CoMSIA). Models of comparative statistical significance were obtained. Field contribution maps were produced for the different models. Due to cutoff settings in the CoMFA fields and the steepness of the potentials close to the molecular surface, the CoMFA maps are often rather fragmentary and not contiguously connected. This makes their interpretation difficult. The maps obtained by the new CoMSIA approach are superior and easier to interpret. Whereas the CoMFA maps denote regions apart from the molecules where interactions with a putative environment are to be expected, the CoMSIA maps highlight those regions within the area occupied by the ligand skeletons that require a particular physicochemical property important for activity. This is a more significant guide to trace the features that really matter especially with respect to the design of novel compounds.
Isolation and structure determination of the main related substances of teicoplanin, a glycopeptide antibiotic. (1988)

Teicoplanin is a complex formed by five closely related glycopeptides and by a small amount of a hydrolysis product. Minor quantities of related substances are also present. Two of them (named RS-1 and RS-2) were isolated and purified starting from the tailing fractions of a teicoplanin batch. Preparative reversed-phase liquid chromatography on large low-pressure and medium high-pressure scales, concentration, desalting, and freeze-drying steps were applied. 300 mg of RS-1 and 900 mg of RS-2 were obtained in a purity grade (about 90%) sufficient for structural investigation. Starting from considerations on the HPLC retentivity and on biosynthesis, the structures were assigned on the basis of 1H-N.M.R. spectra and homonuclear CO-SY 2D experiments, FAB-MS spectrometry, and GC-MS of the esters of the fatty acids obtained by hydrolysis. RS-1 and RS-2 are teicoplanins having 10-methyl-undecanoic acid and n-dodecanoic acid, respectively as fatty acid chains. No major difference in the in vitro activity of these teicoplanins emerged in comparison with teicoplanin complex.
Bifidobacterium breve Attenuates Murine Dextran Sodium Sulfate-Induced Colitis and Increases Regulatory T Cell Responses (2014)

While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus) and Bifidobacterium breve (B. breve) on T cell polarization in vitro, using human peripheral blood mononuclear cells (PBMC), and in vivo, using murine dextran sodium sulfate (DSS) colitis model. With respect to the latter, the mRNA expression of T cell subset-associated transcription factors and cytokines in the colon was measured and the T helper type (Th) 17 and regulatory T cell (Treg) subsets were determined in the Peyer's patches. Both L. rhamnosus and B. breve incubations in vitro reduced Th17 and increased Th2 cell subsets in human PBMCs. In addition, B. breve incubation was also able to reduce Th1 and increase Treg cell subsets in contrast to L. rhamnosus. In vivo intervention with B. breve, but not L. rhamnosus, significantly attenuated the severity of DSS-induced colitis. In DSS-treated C57BL/6 mice, intervention with B. breve increased the expression of mRNA encoding for Th2- and Treg-associated cytokines in the distal colon. In addition, intervention with B. breve led to increases of Treg and decreases of Th17 cell subsets in Peyer's patches of DSS-treated mice. B. breve modulates T cell polarization towards Th2 and Treg cell-associated responses in vitro and in vivo. In vivo B. breve intervention ameliorates DSS-induced colitis symptoms and this protective effect may mediated by its effects on the T-cell composition.
Formation of Supported Membranes from Vesicles (2000)

Using a combination of the quartz crystal microbalance and surface plasmon resonance techniques, we have studied the spontaneous formation of supported lipid bilayers from small (approximately 25 nm) unilamellar vesicles. Together these experimental methods measure the amount of lipid adsorbed on the surface and the amount of water trapped by the lipid. With this approach, we have, for the first time, been able to observe in detail the progression from the adsorption of intact vesicles to rupture and bilayer formation. Monte Carlo simulations reproduce the data.