gebhart/patrepeval huggingface dataset:
Thymocytes may persist and differentiate without any input from bone marrow progenitors (2012)

Thymus transplants can correct deficiencies of the thymus epithelium caused by the complete DiGeorge syndrome or FOXN1 mutations. However, thymus transplants were never used to correct T cell-intrinsic deficiencies because it is generally believed that thymocytes have short intrinsic lifespans. This notion is based on thymus transplantation experiments where it was shown that thymus-resident cells were rapidly replaced by progenitors originating in the bone marrow. In contrast, here we show that neonatal thymi transplanted into interleukin 7 receptor-deficient hosts harbor populations with extensive capacity to self-renew, and maintain continuous thymocyte generation and export. These thymus transplants reconstitute the full diversity of peripheral T cell repertoires one month after surgery, which is the earliest time point studied. Moreover, transplantation experiments performed across major histocompatibility barriers show that allogeneic transplanted thymi are not rejected, and allogeneic cells do not induce graft-versus-host disease; transplants induced partial or total protection to infection. These results challenge the current dogma that thymocytes cannot self-renew, and indicate a potential use of neonatal thymus transplants to correct T cell-intrinsic deficiencies. Finally, as found with mature T cells, they show that thymocyte survival is determined by the competition between incoming progenitors and resident cells.
Hemifluorinated surfactants: a non‐dissociating environment for handling membrane proteins in aqueous solutions? (2004)

The instability of membrane proteins in detergent solution can generally be traced to the dissociating character of detergents and often correlates with delipidation. We examine here the possibility of substituting detergents, after membrane proteins have been solubilized, with non-detergent surfactants whose hydrophobic moiety contains a perfluorinated region that makes it lipophobic. In order to improve its affinity for the protein surface, the fluorinated chain is terminated by an ethyl group. Test proteins included bacteriorhodopsin, the cytochrome b(6)f complex, and the transmembrane region of the bacterial outer membrane protein OmpA. All three proteins were purified using classical detergents and transferred into solutions of C(2)H(5)C(6)F(12)C(2)H(4)-S-poly-Tris-(hydroxymethyl)aminomethane (HF-TAC). Transfer to HF-TAC maintained the native state of the proteins and prevented their precipitation. Provided the concentration of HF-TAC was high enough, HF-TAC/membrane protein complexes ran as single bands upon centrifugation in sucrose gradients. Bacteriorhodopsin and the cytochrome b(6)f complex, both of which are detergent-sensitive, exhibited increased biochemical stability upon extended storage in the presence of a high concentration of HF-TAC as compared to detergent micelles. The stabilization of cytochrome b(6)f is at least partly due to a better retention of protein-bound lipids.
The Effects of Different Frequency Responses on Sound Quality Judgments and Speech Intelligibility (1988)

Four speech programs and two music programs were reproduced using five different frequency responses: one flat and the others combinations of reductions at lower frequencies and/or increases at higher frequencies. Twelve hearing impaired (HI) and 8 normal hearing (NH) subjects listened monaurally to the reproductions at comfortable listening level and judged the sound quality on seven perceptual scales and a scale for total impression. Speech intelligibility was measured for phonetically balanced (PB) word lists and for sentences in noise. Significant differences among the reproductions appeared in practically all scales. The most preferred system was characterized by a flat response at lower frequencies and a 6 dB/octave increase thereafter. There were certain differences between the NH and HI listeners in the judgments of the other systems. The intelligibility of PB word lists did not differ among the systems, and the S/N threshold for the sentences in noise only distinguished the flat response as worse than all others for the HI listeners. There was little correspondence between intelligibility measures and sound quality measures. The latter provided more information and distinctions among systems.
Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells (1996)

We have previously shown that tumor necrosis factor (TNF)alpha strongly potentiates the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3-dependent proliferation of CD34+ hematopoietic progenitor cells (HPC) through the recruitment of early progenitors with high proliferative potential. Furthermore, the combination of GM-CSF and TNFalpha allows the generation of large numbers of dendritic/Langerhans cells (D-Lc). Herein, we analyzed whether IL-3, when combined to TNFalpha would, as does GM-CSF, allow the generation of CD1a+ D-Lc. Accordingly, cultures of cord blood CD34+ HPC with IL-3 + TNFalpha yielded 20% to 60% CD14+ cells and 11% to 17% CD1a+ cells, while IL-3 alone did not generate significant numbers of CD1a+ cells. Although the percentage of CD1a+ cells detected in IL3 + TNFalpha was lower than that observed in GM-CSF + TNFalpha (42% to 78%), the strong growth induced by IL-3 + TNFalpha generated as many CD1a+ cells as did GM-CSF + TNFalpha. The CD14+ and CD1a+ cells generated with IL-3 + TNFalpha are similar to CD14+ and CD1a+ cells generated in GM-CSF alone and GM-CSF + TNFalpha, respectively. CD1a+ cells differed from CD14+ cells by (1) dendritic morphology, (2) higher expression of CD1a, CD1c, CD4, CD40, adhesion molecules (CD11c, CD54, CD58), major histocompatibility complex (MHC) class II molecules and CD28 ligands (CD80 and CD86), (3) lack of Fc receptor FcgammaRI (CD64) and complement receptor CR1 (CD35) expression, and (4) stronger induction of allogeneic T-cell proliferation. Thus, in combination with TNFalpha, IL-3 is as potent as GM-CSF for the generation of CD1a+ D-Lc from cord blood CD34+ HPC. The dendritic cell inducing ability of IL-3 may explain why mice with inactivated GM-CSF gene display dendritic cells.
Detection of U.S., Lelystad, and European-Like Porcine Reproductive and Respiratory Syndrome Viruses and Relative Quantitation in Boar Semen and Serum Samples by Real-Time PCR (2004)

Transmission of porcine reproductive and respiratory syndrome virus (PRRSV) via boar semen has been documented. Since semen is widely disseminated for artificial insemination and the virus can cause significant health and economic consequences, it is essential to have well-validated, rapid diagnostic techniques to detect and quantitate the virus for diagnostic and research purposes. Previously, boar semen was tested by a nested PCR (nPCR) assay which was compared to the "gold standard" swine bioassay. A correlation of 94% was observed, indicating that, most of the time, PCR detected infectious virus. Subsequently, a real-time PCR targeting the 3' untranslated region of the PRRSV genome was compared with nPCR by testing 413 serum and semen samples from PRRSV-inoculated and control boars. There was 95% agreement between the results of the two tests, with the majority of samples with discordant results containing virus at the lower range of detection by the assays. The virus in all samples was quantitated by using a standard curve obtained by serial dilution of an in vitro transcript. By using the in vitro transcript, the lower limit of sensitivity was observed to be approximately 33 copies/ml. Reactivity with a panel of more than 100 PRRSV isolates from various geographical regions in the United States was also documented. No reactivity with nine nonrelated swine viruses was noted. A real-time PCR was also developed for the detection of the European Lelystad virus and the European-like PRRSV now found in the United States. In six of six PRRSV-inoculated boars, peak levels of viremia occurred at 5 days postinoculation (DPI) and were most consistently detectable throughout 22 DPI. In five of six boars, PRRSV was shed in semen for 0 to 2 days during the first 10 DPI; however, one of six boars shed the virus in semen through 32 DPI. Therefore, in general, the concentration and duration of PRRSV shedding in semen did not correlate with the quantity or duration of virus in serum. These differences warrant further studies into the factors that prevent viral replication in the reproductive tract.
Inhibitors of Cyclin Dependent Kinases: Useful Targets for Cancer Treatment (2008)

Cancer drug discovery is one of the most rapidly changing areas of pharmaceutical research. Uncontrolled proliferation is a hallmark of cancer cells. Over the past two decades, it has become increasingly clear that in many human cancers, hyperactivity of Cyclin Dependent Kinases (CDKs) is one of the mechanisms underlying the physiological hyper-proliferation. CDKs are serine/threonine protein kinases, which play an important role in cell-cycle regulation. Their sequential activation ensures, the correct timing and ordering of events required for cell cycle progression. Therefore, inhibition of CDKs, through the insertion of small molecules into its ATP binding pocket has emerged as a potential therapy method for cancers. Consequently, a number of small molecules with CDK inhibitory properties have been developed. Many of these have been evaluated as potent inhibitors and some are currently in clinical-trials for various types of cancer. This review reports various CDK inhibitors, natural as well as small molecules, along with their reported activities for various CDKs. It will highlight the potential for the development of novel anti-cancer molecules.
Single Quantum-Dot-Based Aptameric Nanosensor for Cocaine (2009)

Recent advances in single-molecule detection, nanotechnology, and aptameric sensors hold exciting promise for many potential applications. By functionalizing the surface of a quantum dot (QD) with aptamers which can recognize cocaine, and taking advantage of single-molecule detection and fluorescence resonance energy transfer (FRET) between 605QD and Cy5 and Iowa Black RQ, we develop a single-QD-based aptameric sensor that is capable of sensing the presence of cocaine through both signal-off and signal-on modes. In comparison with the established aptameric sensors, this single-QD-based aptameric sensor has the significant advantages of simple sample preparation, high sensitivity, and extremely low sample consumption. With the advances in the development of varieties of aptamers for small molecules, nucleic acids, metal ions, and proteins, this single-QD-based aptameric sensor might find wide application in forensic analysis, environmental monitoring, and clinic diagnostics.
Early Clostridium difficile Infection during Allogeneic Hematopoietic Stem Cell Transplantation (2014)

Clostridium difficile infection (CDI) is frequently diagnosed in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We characterized early-transplant CDI and its associations, and analyzed serially-collected feces to determine intestinal carriage of toxigenic C. difficile. Fecal specimens were collected longitudinally from 94 patients during allo-HSCT hospitalization, from the start of pre-transplant conditioning until up to 35 days after stem cell infusion. Presence of C. difficile 16S rRNA and tcdB genes was determined. Clinical variables and specimen data were analyzed for association with development of CDI. Historical data from an additional 1144 allo-HSCT patients was also used. Fecal specimens from 37 patients (39%) were found to harbor C. difficile. Early-transplant CDI was diagnosed in 16 of 94 (17%) patients undergoing allo-HSCT; cases were generally mild and resembled non-CDI diarrhea associated with transplant conditioning. CDI was associated with preceding colonization with tcdB-positive C. difficile and conditioning regimen intensity. We found no associations between early-transplant CDI and graft-versus-host disease or CDI later in transplant. CDI occurs with high frequency during the early phase of allo-HSCT, where recipients are pre-colonized with toxigenic C. difficile. During this time, CDI incidence peaks during pre-transplant conditioning, and is correlated to intensity of the treatment. In this unique setting, high rates of CDI may be explained by prior colonization and chemotherapy; however, cases were generally mild and resembled non-infectious diarrhea due to conditioning, raising concerns of misdiagnosis. Further study of this unique population with more discriminating CDI diagnostic tests are warranted.
A Discussion of Sampling Theorems (1959)

The convolution theorem of Fourier analysis is a convenient tool for the derivation of a number of sampling theorems. This approach has been used by several authors to discuss first-order sampling of functions whose spectrum is limited to a region including the origin ("low-pass" functions). The present paper extends this technique to several other cases: second-order sampling of low-pass and band-pass functions, quadrature and Hilbert-transform sampling, sampling of periodic functions, and simultaneous sampling of a function and of one or more of its derivatives.
Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery (2014)

For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tumor metabolite 2-hydroxyglutarate (2-HG) from tissue sections of surgically resected gliomas, under ambient conditions and without complex or time-consuming preparation. With DESI MS, we identify isocitrate dehydrogenase 1-mutant tumors with both high sensitivity and specificity within minutes, immediately providing critical diagnostic, prognostic, and predictive information. Imaging tissue sections with DESI MS shows that the 2-HG signal overlaps with areas of tumor and that 2-HG levels correlate with tumor content, thereby indicating tumor margins. Mapping the 2-HG signal onto 3D MRI reconstructions of tumors allows the integration of molecular and radiologic information for enhanced clinical decision making. We also validate the methodology and its deployment in the operating room: We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite and demonstrate the molecular analysis of surgical tissue during brain surgery. This work indicates that metabolite-imaging MS could transform many aspects of surgical care.
SM16, an Orally Active TGF-β Type I Receptor Inhibitor Prevents Myofibroblast Induction and Vascular Fibrosis in the Rat Carotid Injury Model (2008)

These results are the first to demonstrate the efficacy of an orally active, small-molecule ALK5/ALK4 inhibitor in a vascular fibrosis model and suggest the potential therapeutic application of these inhibitors in vascular fibrosis.
Electric Properties of Zinc Oxide Epitaxial Films Grown by Ion-Beam Sputtering with Oxygen-Radical Irradiation (1999)

Undoped and aluminum-doped ZnO epitaxial films were grown on (001) sapphire substrates by an ion-beam sputtering method with or without the irradiation of oxygen radicals. The effect of oxygen-radical irradiation was notable in the undoped ZnO films when the growth temperature was relatively low. The irradiation improved the crystallinity and decreased the oxygen-vacancy concentration, while it induced internal stress into the films. The carrier concentration of the undoped ZnO films was decreased by the oxygen-radical irradiation, which was attributable to a decrease in the oxygen-vacancy concentration. The Hall mobility of the undoped ZnO films was as low as 1–3 cm 2 V -1 s -1 . The low mobility was explained by carrier scattering due to the potential barriers at the grain boundaries. The height of the potential barriers at the grain boundaries decreased with increasing carrier concentration. This behavior was well explained by a simple model assuming a single defect state at grain boundaries.
Antagonistic effects of systemic interleukin 2 on immune Tcell-mediated graft-versus-leukemia reactivity. (1998)

This study demonstrates that systemic interleukin 2 (IL-2) can decrease the homing of syngeneic immune T cells to the target organ of metastases and accelerate unwanted side effects of allogeneic immune T cells. As a tumor system, we used the well-characterized highly aggressive DBA/2 mouse leukemia ESb and its less aggressive adhesion variant, ESb-MP. Systemic IL-2 treatment was performed with recombinant human interleukin-2 (Proleukin), which was slowly released via an implanted osmotic pump or was modified with polyethylene glycol (PEG-IL-2) to achieve constant plasma levels. Allogeneic B10.D2 antitumor immune spleen cells (ISPL cells) exerted strong graft-versus-leukemia (GvL) reactivity after adoptive transfer into late-stage ESb-MP tumor-bearing DBA/2 mice. Mls(a) superantigen-reactive vbeta6 donor T cells were not eliminated or tolerized by in vivo priming with the tumor cells and were present in active proliferation in liver infiltrates. When exogenous PEG-IL-2 or Proleukin was applied in addition to ISPL cells in such mice, the strong GvL-mediated protective immunity was converted into a fatal graft-versus-host disease. IL-2 treatment alone had no toxic effect and caused a moderate protection effect in the absence of an effect on local tumor growth. Potentiation of GvH reactivity of B10.D2 ISPL by PEG-IL-2 was proven in non-tumor-bearing DBA/2 mice, in which graft-versus-host disease was characterized by: (a) heavy hepatic lymphocytic infiltration, (b) irreversible increase of serum glutamate-oxalacetate-transaminase and glutamate-pyruvate-transaminase levels, (c) weight loss, and (d) death. Antagonistic effects of systemic IL-2 on GvL were observed with syngeneic DBA/2 anti-ESb immune peritoneal effector cells (PECs). There was a detrimental effect of systemic IL-2 on liver target organ infiltration by immune T cells causing, at day 6 after transfer, a drop from 20-30 CD4 or CD8 T cells per liver lobule in the PEC group to <5 in the PEC plus IL-2 group. The results emphasize the importance of a better understanding of IL-2 function in vivo and of its interaction with immune cell function to improve protocols for optimal application in the clinic to achieve maximal GvL effects.
Quantification of Low-Picomolar Concentrations of TNF-α in Serum Using the Dual-Network Microfluidic ELISA Platform (2008)

For both research and diagnostic purposes, the ability to detect low levels of proteins in a cost- and time-effective manner is essential. In this study, the cytokine TNF-alpha (tumor necrosis factor-alpha), a widely used protein indicator of inflammatory response, was chosen to demonstrate the ability of the dual-network microfluidic ELISA (enzyme-linked immunosorbent assay) platform developed by the authors to rapidly quantify low concentrations of this biomarker in serum. Through the optimization of several experimental parameters, the system was shown to meet the requirements for fundamental and applied studies, while also being relevant for challenging clinical applications such as the diagnosis of septic patients. A sensitivity of 45 pg/mL (2.6 pM) in both culture medium and serum, with inter- and intravariations of less than 15%, was attained for the quantification of human TNF-alpha to a concentration of up to 500 pg/mL. The overall time for completion of the assay in eight parallel reactions was less than 1 h.
A Prospective Randomized Trial of Topical Soluble 0.1% Indomethacin Versus 0.1% Diclofenac Versus Placebo for the Control of Pain Following Excimer Laser Photorefractive Keratectomy (1998)

Topical 0.1% indomethacin solution helps control the pain induced by excimer laser photoablation of the cornea without any detrimental effect to the corneal epithelial wound healing.
Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma (1998)

In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.
Amine hydrochlorides by reduction in the presence of chloroform (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmine hydrochlorides by reduction in the presence of chloroformJohn A. Secrist III and Marshall W. LogueCite this: J. Org. Chem. 1972, 37, 2, 335–336Publication Date (Print):January 1, 1972Publication History Published online1 May 2002Published inissue 1 January 1972https://pubs.acs.org/doi/10.1021/jo00967a042https://doi.org/10.1021/jo00967a042research-articleACS PublicationsRequest reuse permissionsArticle Views958Altmetric-Citations89LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts