gebhart/patrepeval huggingface dataset:
Transcriptional Targeting of Retroviral Vectors to the Erythroblastic Progeny of Transduced Hematopoietic Stem Cells (1999)

Targeted expression to specific tissues or cell lineages is a necessary feature of a gene therapy vector for many clinical applications, such as correction of hemoglobinopathies or thalassemias by transplantation of genetically modified hematopoietic stem cells. We developed retroviral vectors in which the constitutive viral enhancer in the U3 region of the 3' LTR is replaced by an autoregulatory enhancer of the erythroid-specific GATA-1 transcription factor gene. The replaced enhancer is propagated to the 5' LTR upon integration into the target cell genome. The modified vectors were used to transduce human hematopoietic cell lines, cord blood-derived CD34(+) stem/progenitor cells, and murine bone marrow repopulating stem cells. The expression of appropriate reporter genes (triangle upLNGFR, EGFP) was analyzed in the differentiated progeny of transduced stem cells in vitro, in liquid culture as well as in clonogenic assay, and in vivo, after bone marrow transplantation in lethally irradiated mice. The GATA-1 autoregulatory enhancer effectively restricts the expression of the LTR-driven proviral transcription unit to the erythroblastic progeny of both human progenitors and mouse-repopulating stem cells. Packaging of viral particles, integration into the target genome, and stability of the integrated provirus are not affected by the LTR modification. Enhancer replacement is therefore an effective strategy to target expression of a retroviral transgene to a specific progeny of transduced hematopoietic stem cells.
The Binding of Factor H to a Complex of Physiological Polyanions and C3b on Cells Is Impaired in Atypical Hemolytic Uremic Syndrome (2009)

Factor H (fH) is essential for complement homeostasis in fluid-phase and on surfaces. Its two C-terminal domains (CCP 19-20) anchor fH to self-surfaces where it prevents C3b amplification in a process requiring its N-terminal four domains. In atypical hemolytic uremic syndrome (aHUS), mutations clustering toward the C terminus of fH may disrupt interactions with surface-associated C3b or polyanions and thereby diminish the ability of fH to regulate complement. To test this, we compared a recombinant protein encompassing CCP 19-20 with 16 mutants. The mutations had only very limited and localized effects on protein structure. Although we found four aHUS-linked fH mutations that decreased binding to C3b and/or to heparin (a model compound for cell surface polyanionic carbohydrates), we identified five aHUS-associated mutants with increased affinity for either or both ligands. Strikingly, these variable affinities for the individual ligands did not correlate with the extent to which all the aHUS-associated mutants were found to be impaired in a more physiological assay that measured their ability to inhibit cell surface complement functions of full-length fH. Taken together, our data suggest that disruption of a complex fH-self-surface recognition process, involving a balance of affinities for protein and physiological carbohydrate ligands, predisposes to aHUS.
Hemolytic Transfusion Reactions (2008)

SUMMARY: The risk of hemolytic transfusion reactions (HTRs) is approximately 1:70,000 per unit. Acute HTRs occurring during or within 24 h after administration of a blood product are usually caused by transfusion of incompatible red blood cells (RBCs), and, more rarely, of a large volume of incompatible plasma. Delayed HTRs are caused by a secondary immune response to an antigen on the donor's RBCs. In some patients with delayed HTRs, an additional bystander hemolysis of the patient's RBCs can be assumed. Different mechanisms lead to intra- and extra-vascular hemolysis, such as complete complement activation, phagocytosis of RBCs covered with C3b by macrophages after incomplete complement activation, or destruction of RBCs covered only with IgG by direct cell-cell contact with K cells. The clinical consequences of HTRs are triggered via several pathophysiological pathways like formation of anaphylatoxins, release of cytokines causing a systemic inflammatory response syndrome, activation of the kinin system, the intrinsic clotting cascade and fibrinolysis resulting in hypotension, disseminated intravascular coagulation, diffuse bleeding, and disruption of microcirculation leading to renal failure and shock. In the following, the symptoms of HTR are introduced, laboratory investigations and treatment are described, and some recommendations for prevention are given.
Comparison of bioanalytical determinations of Iloprost, a chemically stable PGI2 mimetic, by conventional radioimmunoassay (RIA) and scintillation proximity assay (SPA). (1992)

The scintillation proximity assay is a novel variant of classical radioimmunoassay. It can be performed as a single tube measurement because the separation of bound and unbound tracer fraction is avoided. In principle, microbeads are coated with anti-species antibodies that can couple with the respective antiserum used for RIA. By means of special cores, light emission takes place if labelled, antiserum-bound tracer is coupled to the anti-species antibody on the fluomicrosphere surface. In the present report, the novel assay was compared to a validated RIA for the bioanalysis of the PGI2 mimetic, Iloprost. Extraction recovery of Iloprost was approximately 90% at pH less than or equal to 4. The detection limit of the novel assay was 2-4 pg/sample, corresponding to 10-20 pg/ml plasma (if 0.2 ml plasma was used). Coefficients of variations were 9, 7 and 6% (within-day, n = 5) and 30, 11 and 10% (day-to-day, n = 10) at 50, 100 and 200 pg/ml. RIA and SPA levels of Iloprost measured in human plasma samples (n = 428) were similar. The SPA method exhibits both a similar specificity and detection limit to RIA and will be used for further analyses.
Association between prostate cancer and serum testosterone levels (2002)

Our findings show that serum total and free testosterone levels in patients with prostate cancer are altered, supporting the possibility that prostate cancer may inhibit serum testosterone levels.
An extended RNA/RNA duplex structure within the coding region of mRNA does not block translational elongation (1988)

RNA/RNA duplex formation involving the 5'untranslated region of a mRNA can efficiently block translation. Here we investigated the effect on translation of an RNA/RNA duplex between part of the coding region and sequences of the 3'untranslated region of lysozyme mRNA. A cDNA was constructed which contained 2 identical sequences of 150 nucleotides, one of which was an inverted repeat of the other. Cell-free transcription of this cDNA with T7 RNA polymerase resulted in a mRNA with an extended RNA/RNA duplex within the coding region. The presence of the double stranded structure was confirmed by the accessibility of complementary oligonucleotides to this region. mRNA was cleaved by RNaseH, endogenous to the wheat germ lysate, when hybridization of a complementary oligonucleotide occurred outside but not within the predicted double stranded structure. When this mRNA was translated in a cell-free wheat germ translation system, the translation product was found to be of the size of full-length prelysozyme and not arrested. We conclude that the extend of a secondary structure within the coding region of a mRNA does not restrict the ability of the ribosome to translate this mRNA efficiently. Our data are consistent with the presence of an activity unwinding RNA/RNA duplexes, which is associated with the translating ribosome.
A colour display technique for NMR imaging (1977)

&lt;p&gt;Convergent systems are systems that have a uniquely defined globally asymptotically stable steady-state solution. Asymptotically stable linear systems excited by a bounded time varying signal are convergent. Together with the superposition principle, the convergence property forms a foundation for a large number of analysis and (control) design tools for linear systems. Nonlinear convergent systems are in many ways similar to linear systems and are, therefore, in a certain sense simple, although the superposition principle does not hold. This simplicity allows one to solve a number of analysis and design problems for nonlinear systems and makes the convergence property highly instrumental for practical applications. In this chapter, we review the notion of convergent systems and its applications to various analyses and design problems within the field of systems and control.&lt;/p&gt;
Synthesis of 3'-azido-2',3'-dideoxyribofuranosylpurines (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 3'-azido-2',3'-dideoxyribofuranosylpurinesM. Imazawa and F. EcksteinCite this: J. Org. Chem. 1978, 43, 15, 3044–3048Publication Date (Print):July 1, 1978Publication History Published online1 May 2002Published inissue 1 July 1978https://pubs.acs.org/doi/10.1021/jo00409a024https://doi.org/10.1021/jo00409a024research-articleACS PublicationsRequest reuse permissionsArticle Views382Altmetric-Citations64LEARN 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
Metastatic Breast Tumour Regression Following Treatment by a Gene‐Modified Vaccinia Virus Expressing MUC1 and IL‐2 (2003)

MUC1 is expressed by glandular epithelial cells. It is overexpressed in the majority of breast tumours, making it a potential target for immune therapy. The objectives of the present study were to evaluate the anti‐tumour activity and tolerance of repeated administration of TG1031 (an attenuated recombinant vaccinia virus containing sequences coding for human MUC1 and the immune stimulatory cytokine IL‐2) in patients with MUC1‐positive metastatic breast cancer. This was an open‐label, randomised study comparing two dose levels, 5 × 10E6 and 5 × 10E7 pfu, with 14 patients in each arm. The treatment was administered intramuscularly every 3 weeks for the first 4 doses and every 6 weeks thereafter, until progression. Two patients had a partial tumour regression (&gt;50%), and 15 patients had stable disease as their best overall response until at least the 5th injection. Partial regression lasted for 11 months in one patient and for 12 months in the second patient who then underwent surgical resection of her hepatic metastases. The most frequent adverse events included inflammation at injection site: 7 patients, itching or pain at injection site: 5 patients, and moderate fever: 6 patients. One responding patient developed antinuclear, anti‐DNA, and increased anti‐TPO antibodies after the fifth injection, and which resolved at the end of treatment. The treatment regimes were well tolerated with a low toxicity profile. Although clinical efficacy remains limited, this study demonstrates the potential use of MUC1‐based immune therapy in breast cancer.
A rapid plate assay for screening l ‐asparaginase producing micro‐organisms (1997)

A pH and dye-based fast procedure for screening L-asparaginase producing micro-organisms is reported. The procedure is suitable for bacterial and fungal screening. The results are obtained within 24 and 48 h for bacteria and fungi, respectively. The results correlate with quantitative estimations in culture broths.
Development of venetoclax for therapy of lymphoid malignancies (2017)

B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients. Also, unlike the other targeted agents, it is effective against tumor cells that reside in the blood marrow. Despite its promising outcome in CLL, preclinical data have already uncovered mechanistic insights underlying venetoclax resistance, such as upregulation of MCL-1 or BCL-xL expression and protective signaling from the microenvironment. In this review, we describe the role of the BCL-2 family in the pathogenesis of B-cell lymphoid malignancies, the development of venetoclax, and its current clinical outcome in CLL and other B-cell malignancies. We also discuss the resistance mechanisms that develop following venetoclax therapy, potential strategies to overcome them, and how this knowledge can be translated into clinical applications.
Substrate Current due to Impact Ionization in MOS-FET (1976)

The substrate leakage current vs. gate voltage characteristics of MOS-FET was examined over a wide range of device parameters and measurement conditions. With the increase in the gate voltage, the substrate current increases until it reaches a maximum value. Then it decreases to the value of the generation-recombination current. The substrate current has a high value at low measurement temperatures, high drain voltages, high impurity concentrations of silicon substrates, thin gate-oxide thicknesses and a large drain current. These experimental results were semi-quantitatively explained on the basis of a model in which the substrate current is caused by the first-order impact ionization of the carriers within the pinched-off region. The observed increase of the substrate current is mainly dominated by an increase of the drain current, and the decrease of the substrate current is mainly dominated by a decrease of the impact ionization coefficient.
System trade analysis for an ultra-wideband forward imaging radar (2006)

In support of the U.S. Army vision for increased mobility, survivability, and lethality, the Army Research Laboratory is currently developing a new version of the low frequency ultra-wideband (UWB) synthetic aperture radar (SAR) to support forward imaging. One of the goals in the development of this version of the radar is to make it affordable. This paper presents a study of various forward imaging radar configurations that could be employed in a forward imaging radar system to achieve good imaging resolution with a reasonable number of transmitters/receivers. This study provided us with insights to efficiently configure our transmitter/receiver array. In this study, we examined various radar configurations such as monostatic and some variations of bistatic cases. We provide the analysis of the synthetic aperture radar (SAR) image resolution for these configurations and show the effectiveness of the bistatic configuration with only two transmitters at the ends of the physical array. In addition to the analysis, we also provide simulation results to demonstrate the expected imaging resolutions with respect to the radar configuration and the imaging geometry. Finally, we also consider the use of two squinted transmitters at the two ends and exploit the forward motion of the vehicle to form image on the two sides.
Ultra wide band supercontinuum generation in air-silica holey fibers by SHG-induced modulation instabilities (2005)

Second harmonic generation in an air-silica microstructured optical fiber pumped by subnanosecond pulses is used in order to initiate modulation instability processes in normal and anomalous dispersion regimes. This allows us to generate an ultra wide and flat supercontinuum (350-1750 nm), covering the entire transparency window of silica and exhibiting a singlemode transverse profile in visible range.
Group IV phosphinimide amide complexes (2004)

Complexes of formula TiCp(NPR 3 )(NMe 2 ) 2 (R = t-Bu 1, Ph 2) were prepared via salt metathesis of TiCp(NPR 3 )Cl 2 with a slight excess of LiNMe 2 . The species Ti(NP-t-Bu 3 )(NMe 2 ) 3 (3) was obtained as a by-product. The related derivative ZrCp(NP-t-Bu 3 )(NMe 2 ) 2 (4) was also prepared. Reaction of TiCp(NP-t-Bu 3 )Cl 2 with LiNHC 6 H 3 (2,6-i-Pr 2 ) afforded TiCp(NP-t-Bu 3 )(NHC 6 H 3 (2,6-i-Pr 2 ))Cl (5) and Ti(NP-t-Bu 3 )(NHC 6 H 3 (2,6-i-Pr 2 )) 3 (6). In a similar manner, the Zr analogs ZrCp(NP-t-Bu 3 )(NHC 6 H 3 (2,6-i-Pr 2 ))Me (7) and ZrCp(NP-t-Bu 3 )(NHC 6 H 3 (2,6-i-Pr 2 )) 2 (8) were also prepared. X-ray structural data for compounds 5, 6, and 8 are reported. Reactivity of these phosphinimideamide derivatives was explored. While these species do not yield imide derivatives upon thermolysis, reaction of 5 with excess AlMe 3 afforded TiCp(NP-t-Bu 3 )Me 2 while reaction with 1 equiv. of AlMe 3 gave TiCp(NP-t-Bu 3 )MeCl (9) and Al 2 (m-NHC 6 H 3 (2,6-i-Pr 2 )) 2 Me 4 (10). Key words: titanium, zirconium, phosphinimide, amide, ligand metathesis.
Di‐, tri‐ and tetrameric single chain Fv antibody fragments against human CD19: effect of valency on cell binding (1999)

Single chain variable fragments (scFv) of the murine monoclonal antibody HD37 specific to human B-cell antigen CD19 were constructed by joining the VH and VL domains with linkers of 18, 10, 1 and 0 residues. ScFv-18 formed monomers, dimers and small amounts of tetramers; scFv-10 formed dimers and small amounts of tetramers; scFv-1 formed exclusively tetramers; scFv-0 formed exclusively trimers. The affinities of the scFv-10 (diabody) and scFv-1 (tetrabody) were approximately 1.5- and 2.5-fold higher, respectively, than that of the scFv-0 (triabody). The tetrabody displayed a significantly prolonged association with cell-bound antigen (t1/2 cell surface retention at 37 degrees C of 26.6 min) compared to both the diabody (13.3 min) and triabody (6.7 min). This increase in avidity of the tetrabody combined with its larger size could prove to be particularly advantageous for imaging and the immunotherapy of B-cell malignancies.
A Switch from E-Cadherin to N-Cadherin Expression Indicates Epithelial to Mesenchymal Transition and Is of Strong and Independent Importance for the Progress of Prostate Cancer (2007)

These novel data unravel the importance of epithelial to mesenchymal transition for prostate cancer progression, and demonstration of a switch from E-cadherin to N-cadherin expression could have significant effect on the care of prostate cancer patients.
Time-frequency MEG-MUSIC algorithm (1999)

We propose a method that incorporates the time-frequency characteristics of neural sources into magnetoencephalographic (MEG) source estimation. The method is based on the multiple-signal-classification (MUSIC) algorithm and it calculates a time--frequency matrix in which diagonal and off-diagonal terms are the auto and crosstime--frequency distributions of multichannel MEG recordings, respectively. The method averages this time-frequency matrix over the time--frequency region of interest. The locations of neural sources are then estimated by checking the orthogonality between the noise subspace of this averaged matrix and the sensor lead field. Accordingly, the method allows us to estimate the locations of neural sources from each time--frequency component. A computer simulation was performed to test the validity of the proposed method, and the results demonstrate its effectiveness.
Active global localization for a mobile robot using multiple hypothesis tracking (2001)

We present a probabilistic approach for mobile robot localization using an incomplete topological world model. The method, called the multi-hypothesis localization (MHL), uses multi-hypothesis Kalman filter based pose tracking combined with a probabilistic formulation of hypothesis correctness to generate and track Gaussian pose hypotheses online. Apart from a lower computational complexity, this approach has the advantage over traditional grid based methods that incomplete and topological world model information can be utilized. Furthermore, the method generates movement commands for the platform to enhance the gathering of information for the pose estimation process. Extensive experiments are presented from two different environments, a typical office environment and an old hospital building.
Pattern recognition receptors and differentiation antigens define murine myeloid cell heterogeneity ex vivo (2003)

Recruitment of myeloid cells during inflammatory reactions plays an important role in the propagation and resolution of inflammation. However, the identification and characterization of these cells in mice has been hampered by cellular heterogeneity at the functional and phenotypic level. We have defined criteria for the rapid flow-cytometric identification of monocytes (M(o)), macrophages (MPhi), neutrophils (N(eu)) and eosinophils (E(os)) in murine tissues using novel and established myeloid markers. These criteria were applied to the study of naive mice and mice with experimentally induced inflammation, both local and systemic, and also to a murine model of tumor progression. We show that the murine 7/4 antigen and the beta-glucan receptor, Dectin-1, are particularly useful for the sub-division of myeloid cells into individual populations, even when inflammatory conditions modulate their surface expression. Furthermore, 7/4 expression allows distinction between M(o) recently recruited to a site and the resident cells already present. These studies highlight the heterogeneity of the murine M(o)/MPhi-lineage, define an extended phenotype for murine myeloid cells and greatly facilitate the ex vivo characterization of these cells during very different models of inflammation.
Subspace-based techniques for blind separation of convolutive mixtures with temporally correlated sources (1997)

This contribution addresses the blind identification of multiple input multiple output linear finite impulse response systems having a number of inputs less than the number of outputs. Recent publications have proposed an efficient second-order identification method in the single input multiple output case. Based on a subspace analysis, it allows a perfect recovery of the system parameters and excitation in a noise-free environment. Some extensions to the case of multiple inputs are also available under quite specific conditions. In this paper we indicate how to extend the original subspace-based approach to the general case.