gebhart/patrepeval huggingface dataset:
A simplified method for enrichment of mouse hematopoietic stem cells. (1990)

A simplified method for enriching mouse hematopoietic stem cells using standard two-color fluorescence-activated cell sorting (FACS) has been developed. By eliminating one fluorescence parameter from a previously described four-parameter (three-color) method, FACS enrichment of mouse hematopoietic stem cells to a purity within twofold of that accomplished by the more complex method could be achieved using a single-laser, two-color FACS instrument. The method involves positive selection of mouse bone marrow cells expressing the Ly-6A.2 molecule (previously termed stem cell antigen-1, or Sca-1) and negative selection for expression of a number of cell surface markers characteristic of differentiated cells of hematolymphoid lineages (Lin-). Cell populations selected by this method contain 480 +/- 100 day-13 splenic colony-forming units (CFUs-13) per 10(4) cells, whereas the day-8 splenic colony-forming unit (CFUs-8) content is about tenfold lower. The frequency of thymic colony-forming units (CFUt) is about one in ten cells. Long-term hematopoietic repopulation of irradiated animals was observed following the transfer of 60-100 cells. However, as few as 20 cells could mediate radioprotection of lethally irradiated mice. An analysis of the cell surface phenotype of isolated Ly-6A.2+Lin- cells showed that 30%-50% expressed low levels of the Thy-1 antigen and that the CFUs-13 activity was predominantly associated with the Thy-1lo cells. The Ly-6A.2+Lin- cells expressed intermediate levels of phagocyte glycoprotein-1 (Pgp-1), low levels of heat-stable antigen (HSA), and high levels of class I major histocompatibility antigens (H2 K/D), leukocyte common antigen (Ly-5), and carbohydrate binding sites for the lectin wheat-germ agglutinin (WGA). By these criteria, Ly-6A.2+Lin- cells are phenotypically similar to mouse hematopoietic stem cells isolated by other methods.
Establishment of an HLA-A*0201 human papillomavirus type 16 tumor model to determine the efficacy of vaccination strategies in HLA-A*0201 transgenic mice. (2002)

With the increasing generation of new cancer vaccine strategies, there is also an increasing demand for preclinical models that can carefully predict the efficacy of these vaccines in humans. However, the only tumor models available to study vaccines against human papillomavirus (HPV) 16 have been developed in C57BL/6 mice. To test the HLA-restricted capabilities of vaccination strategies, it is important to establish a tumor model in HLA-A*0201 transgenic mice. By transfecting heart lung fibroblasts from HLA-A*0201 mice with HPV16 E6 and E7 oncogenes and H-Ras V12, we have generated a transgenic cell line that is tumorigenic in HLA-A*0201 mice. The dominant H-2D(b) HPV16 E7 epitope was removed from the E7 construct to ensure that all antitumor responses were mediated through the HLA-A*0201-restricted epitopes. We used this tumor model to test the efficacy of two genetic vaccines: a plasmid DNA multi-epitope vaccine encoding human epitopes of HPV16, and a Venezuelan equine encephalitis (VEE) virus-based vector to deliver HPV16 E6 and E7 RNA. We show that both our multi-epitope DNA- and VEE-based vaccines protect 100% of HLA-A*0201 transgenic mice from tumor challenge and elicit a specific T-cell response against multiple HLA-A*0201-restricted HPV16 epitopes. Furthermore, both vaccines significantly decreased tumor burden when tested therapeutically. In conclusion, this is the first tumor model that allows for the assessment of the potential of a vaccine to induce HPV-directed, HLA-A*0201-restricted, antitumor responses in mice. These results pave the way for the clinical evaluation of these vaccines.
Myocardial regeneration by embryonic stem cell transplantation: present and future trends (2006)

Embryonic stem cells are a promising source for myocardial regeneration due to their pluripotency and plasticity. In theory, embryonic stem cells are capable of self-renewal in an unlimited fashion, and can differentiate into any cell type required for cell-based therapy, including cardiac myocytes. In recent years, embryonic stem cells have been transplanted for cardiac regeneration in animal models, and the results are encouraging. However, there are still many hurdles to be overcome for the clinical application of embryonic stem cells.
Terrestrial DVB (DVB-T): A Broadcast Technology for Stationary Portable and Mobile Use (2006)

Digital video broadcasting-terrestrial (DVB-T) is the name of the terrestrial transmission system which was developed by the DVB Project. DVB-T is in operation in many countries around the world. This paper analyzes the features of the system. It describes its capabilities with a special emphasis on mobile reception and looks at the introduction of DVB-T in Germany using the launch of DVB-T in this country as a case study. In order to analyze how an MPEG transport stream at the input of a DVB-T modulator is turned into a DVB-T signal, we consider the channel coding and modulation used. Then we look at various aspects of the system performance. The next section deals with mobile reception. Network planning issues, antenna diversity concepts for mobile receivers, and handover procedures will be considered. Finally, the introduction of DVB-T in Germany is presented as a case study. In contrast to various other countries Germany decided to offer DVB-T as a means of providing the "anywhere TV" experience. This implies that DVB-T signals can be received with mobile and portable receivers. In regions with DVB-T coverage analogue terrestrial TV services were discontinued just a few months after the launch of DVB-T.
Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1- O- acetyl-ADP-ribose (2000)

Conflicting reports have suggested that the silent information regulator 2 (SIR2) protein family employs NAD(+) to ADP-ribosylate histones [Tanny, J. C., Dowd, G. J., Huang, J., Hilz, H. & Moazed, D. (1999) Cell 99, 735-745; Frye, R. A. (1999) Biochem. Biophys. Res. Commun. 260, 273-279], deacetylate histones [Landry, J., Sutton, A., Tafrov, S. T., Heller, R. C., Stebbins, J., Pillus, L. & Sternglanz, R. (2000) Proc. Natl. Acad. Sci. USA 97, 5807-5811; Smith, J. S., Brachmann, C. B., Celic, I., Kenna, M. A., Muhammad, S., Starai, V. J., Avalos, J. L., Escalante-Semerena, J. C., Grubmeyer, C., Wolberger, C. & Boeke, J. D. (2000) Proc. Natl. Acad. Sci. USA 97, 6658-6663], or both [Imai, S., Armstrong, C. M., Kaeberlein, M. & Guarente, L. (2000) Nature (London) 403, 795-800]. Uncovering the true enzymatic function of SIR2 is critical to the basic understanding of its cellular function. Therefore, we set out to authenticate the reaction products and to determine the intrinsic catalytic mechanism. We provide direct evidence that the efficient histone/protein deacetylase reaction is tightly coupled to the formation of a previously unidentified acetyl-ADP-ribose product (1-O-acetyl-ADP ribose). One molecule of NAD(+) and one molecule of acetyl-lysine are readily catalyzed to one molecule of deacetylated lysine, nicotinamide, and 1-O-acetyl-ADP-ribose. A unique reaction mechanism involving the attack of enzyme-bound acetate or the direct attack of acetyl-lysine on an oxocarbenium ADP-ribose intermediate is proposed. We suggest that the reported histone/protein ADP-ribosyltransferase activity is a low-efficiency side reaction that can be explained through the partial uncoupling of the intrinsic deacetylation and acetate transfer to ADP-ribose.
Topic Modeling over Short Texts by Incorporating Word Embeddings (2016)

Inferring topics from the overwhelming amount of short texts becomes a critical but challenging task for many content analysis tasks, such as content charactering, user interest profiling, and emerging topic detecting. Existing methods such as probabilistic latent semantic analysis (PLSA) and latent Dirichlet allocation (LDA) cannot solve this prob- lem very well since only very limited word co-occurrence information is available in short texts. This paper studies how to incorporate the external word correlation knowledge into short texts to improve the coherence of topic modeling. Based on recent results in word embeddings that learn se- mantically representations for words from a large corpus, we introduce a novel method, Embedding-based Topic Model (ETM), to learn latent topics from short texts. ETM not only solves the problem of very limited word co-occurrence information by aggregating short texts into long pseudo- texts, but also utilizes a Markov Random Field regularized model that gives correlated words a better chance to be put into the same topic. The experiments on real-world datasets validate the effectiveness of our model comparing with the state-of-the-art models.
Rapid Regulatory T-Cell Response Prevents Cytokine Storm in CD28 Superagonist Treated Mice (2009)

Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of regulatory T-cells (Treg cells) in rats, but a first-in-man trial of the human CD28SA TGN1412 resulted in an unexpected cytokine release syndrome. Using a novel mouse anti-mouse CD28SA, we re-investigate the relationship between Treg activation and systemic cytokine release. Treg activation by CD28SA was highly efficient but depended on paracrine IL-2 from CD28SA-stimulated conventional T-cells. Systemic cytokine levels were innocuous, but depletion of Treg cells prior to CD28SA stimulation led to systemic release of proinflammatory cytokines, indicating that in rodents, Treg cells effectively suppress the inflammatory response. Since the human volunteers of the TGN1412 study were not protected by this mechanism, we also tested whether corticosteroid prophylaxis would be compatible with CD28SA induced Treg activation. We show that neither the expansion nor the functional activation of Treg cells is affected by high-dose dexamethasone sufficient to control systemic cytokine release. Our findings warn that preclinical testing of activating biologicals in rodents may miss cytokine release syndromes due to the rapid and efficacious response of the rodent Treg compartment, and suggest that polyclonal Treg activation is feasible in the presence of antiphlogistic corticosteroid prophylaxis.
Comparison of Caval Filters in the Management of Venous Thromboembolism (1978)

Over a seven-year period, 38 Mobin-Uddin MU and 33 Kim-Ray Greenfield KG vena cava filters were inserted in 71 patients with no substantial complications or deaths directly related to the surgical procedure. Thirteen of the 16 early deaths were due to progression of associated diseases. The remaining three deaths were caused by pulmonary emboli and occurred in each instance after insertion of a MU filter. None of the 14 late deaths were related to the caval filter or sequellae of venous thrombosis. Inferior vena cava patency was objectively assessed in 36 patients by cavagram (22) or autopsy (14). Caval patency of 95% (18 of 19) in those with KG filters was significantly greater than the 47% patency (eight of 17) seen with MU devices (P less than .01). Gray scale ultrasound, when successful in visualizing the vena cava, was found to be a reliable indicator of patency. Venous stasis phenomena were noted in 50% of those with a patent cava and in 70% of those with an occlusion. Thus, it is not surprising that edema was found in only 38% of the patients as compared with 75% of the patients with the MU filter. Both of these devices are safe to insert. However, on the basis of superior patency rate, lower incidence of stasis phenomena, and the absence of recurrent pulmonary emboli in our series, we prefer insertion of a KG filter when caval interruption is required.
Precision Control of CRISPR-Cas9 Using Small Molecules and Light (2019)

The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas system is an adaptive immune system of bacteria that has furnished several RNA-guided DNA endonucleases (e.g., Cas9) that are revolutionizing the field of genome engineering. Cas9 is being used to effect genomic alterations as well as in gene drives, where a particular trait may be propagated through a targeted species population over several generations. The ease of targeting catalytically impaired Cas9 to any genomic loci has led to development of technologies for base editing, chromatin imaging and modeling, epigenetic editing, and gene regulation. Unsurprisingly, Cas9 is being developed for numerous applications in biotechnology and biomedical research and as a gene therapy agent for multiple pathologies. There is a need for precise control of Cas9 activity over several dimensions, including those of dose, time, and space in these applications. Such precision controls, which are required of therapeutic agents, are particularly important for Cas9 as off-target effects, chromosomal translocations, immunogenic response, genotoxicity, and embryonic mosaicism are observed at elevated levels and with prolonged activity of Cas9. Here, we provide a perspective on advances in the precision control of Cas9 over aforementioned dimensions using external stimuli (e.g., small molecules or light) for controlled activation, inhibition, or degradation of Cas9.
STUDY ON ROOT COLONIZATION OF WHEAT BY luxAB GENES-MARKED BACILLUS MEGATERIUM ATCC14581 (2001)

By triparental mating,Bacillus megaterium ATCC14581 strain marked by luxAB gene were successfully obtained,then the ATCC14581-L strain was made to microbial inoculant.After it was inoculated on seeds of wheat,the colonizing dynamics and distribution of the luminescent bacteria ATCC14581-L in the rhizosphere of wheat plant in rhizoboxes were studied by the method of X-ray film imaging and enumeration of luminescent colonies on agar media.The results showed that ATCC14581-L successfully colonized in the rhizosphere of wheat.The population reached to the highest level,2.54×10 5 and 8.87×10 4cfu/g root respectively in the sterile soil and unsterile soil after 7 days,with initial inoculant dose of 3.40×10 7 cfu/g root.The population of them trended to be stable and decreased to 4.47×10 3 and 8.57×10 2 cfu/g root respectively after 16 th day.
Low-Dose 5-Aza-2′-Deoxycytidine, a DNA Hypomethylating Agent, for the Treatment of High-Risk Myelodysplastic Syndrome: A Multicenter Phase II Study in Elderly Patients (2000)

We were able to confirm our previous observation that DAC therapy was effective in half of the studied patients with high-risk myelodysplastic syndrome and is especially active in the patients with the worst prognoses. Myelosuppression was the only major adverse effect observed.
Regulation in S Phase by E2F (2004)

The DNA synthetic S phase of the unperturbed cell cycle is a closed system, as compared to regulation of G(1) by external growth factors. The E2F family provides internal control in S phase by transcribing genes required for deoxynucleotide triphosphate (dNTP) and DNA synthesis. Furthermore, over expression of E2F-1 activates programmed cell death (apoptosis), a safeguarding signal of aberrant growth of cells that have become carcinogenic. Mechanisms for control of E2F-1 are thus essential. The hypothesis is proposed that deoxythymidine triphosphate (dTTP) allosterically feedback controls E2F-1 to regulate both DNA synthesis and apoptosis. This may act either upon production of E2F-1 or its degradation.
Enols of Substituted Cyanomalonamides (2007)

Twenty open-chain mono-, di-, and trialkyl and aryl-N-substituted cyanomalonamides R2R1NCOCH(CN)CONHR3 were prepared. In solution, signals for both amide and a single enol are mostly observed, despite the potential for E and Z isomeric enols. The equilibrium (KEnol) values between the amides and the enols were determined in different solvents by NMR spectra. They decrease on increasing the polarity of the solvent in the order CDCl3 approximately C6D6>THF-d8>(CD3)2CO>CD3CN>DMF-d7>DMSO-d6. For the R1R2NCOCH(CN)CONHR3 system when R1=R2=H, Me or R1=H, R2=Me, KEnol for R3 follows the order: C6F5>Ph>or=An>or= i-Pr>or= t-Bu, and for R1, R2:H, H>Me, H>Me, Me in all solvents. A unique feature is the appreciable % enol in DMSO-d6 when R1=R2=H, in contrast with enol systems with other electron-withdrawing groups (EWGs). Calculations (B3LYP/6-31G**) corroborate the higher KEnol values for less alkyl-substituted systems, showing that in the most stable conformer when R1=H, R2=R3=Me the N-hydrogens are closer to the CN group. The order of promoting substituents for enol of amide formation is CONH2>CO2CH2CF3>CO2Me>CONHMe. The solid-state structures of the isolated species, determined by X-ray crystallography, were either amides or enols, and a higher KEnol(CDCl3) value does not ensure a solid enol structure. In no system were both solid species isolated. The X-ray structures of the enols were temperature-dependent. In most cases, the difference between the O-H and O...H bond lengths at low temperature were appreciable, but they become closer at the higher temperature. Similar tendency for either the C=C/C-C or the C-O/C=O bonds was observed. This is ascribed to a hydrogen shift between two regioisomeric enols in an asymmetric double-well potential, which becomes faster at a higher temperature. Calculations show that the enol structures are nonsymmetrical, resembling the lower temperature structures, even when they are chemically symmetrical, but the energy differences between the two regioisomers are <1 kcal. The hydrogen bonds in the enol moiety are strong, with O...O distances <2.45 A, and are resonance-assisted hydrogen bonds. IR spectra in solution and the solid state qualitatively corroborate the NMR and X-ray structure determination.
Identification of Protein-Protein Interactions and Topologies in Living Cells with Chemical Cross-linking and Mass Spectrometry (2008)

We present results from a novel strategy that enables concurrent identification of protein-protein interactions and topologies in living cells without specific antibodies or genetic manipulations for immuno-/affinity purifications. The strategy consists of (i) a chemical cross-linking reaction: intact cell labeling with a novel class of chemical cross-linkers, protein interaction reporters (PIRs); (ii) two-stage mass spectrometric analysis: stage 1 identification of PIR-labeled proteins and construction of a restricted database by two-dimensional LC/MSMS and stage 2 analysis of PIR-labeled peptides by multiplexed LC/FTICR-MS; and (iii) data analysis: identification of cross-linked peptides and proteins of origin using accurate mass and other constraints. The primary advantage of the PIR approach and distinction from current technology is that protein interactions together with topologies are detected in native biological systems by stabilizing protein complexes with new covalent bonds while the proteins are present in the original cellular environment. Thus, weak or transient interactions or interactions that require properly folded, localized, or membrane-bound proteins can be labeled and identified through the PIR approach. This strategy was applied to Shewanella oneidensis bacterial cells, and initial studies resulted in identification of a set of protein-protein interactions and their contact/binding regions. Furthermore most identified interactions involved membrane proteins, suggesting that the PIR approach is particularly suited for studies of membrane protein-protein interactions, an area under-represented with current widely used approaches.
Treatment for Multiple Myeloma (1969)

Of 183 patients with multiple myeloma treated with melphalan, 43% demonstrated an objective response. Of the evaluable cases, 70% of the patients responded to combination therapy with melphalan and prednisone, 35% to intermittent melphalan therapy, and 19% to daily melphalan therapy. Symptomatic manifestations of disease decreased in almost all responding patients. The degree of remission was superior with melphalan-prednisone therapy since serum myeloma globulin peaks disappeared more frequently from the electrophoresis scan. In patients producing only λ Bence Jones proteins, azotemia was more frequent, the incidence of response was low, and survival was short. Median survival for patients treated with melphalan-prednisone was about six months longer than the survival of patients treated with melphalan alone. Results support the use of intermittent courses of concurrent chemotherapy with large doses of melphalan and prednisone in patients with multiple myeloma.
Evaluation of the Dmt−Tic Pharmacophore:  Conversion of a Potent δ-Opioid Receptor Antagonist into a Potent δ Agonist and Ligands with Mixed Properties (2002)

Analogues of the 2',6'-dimethyl-L-tyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) pharmacophore were prepared to test the hypothesis that a "spacer" and a third aromatic center in opioid peptides are required to convert a delta-antagonist into ligands with delta-agonist or with mixed delta-antagonist/mu-agonist properties. Potent delta-agonists and bifunctional compounds with high delta- and mu-opioid receptor affinities were obtained by varying the spacer length [none, NH-CH(2), NH-CH(2)-CH(2), Gly-NH-CH(2)] and C-terminal aromatic nucleus [1H-benzimidazole-2-yl, phenyl (Ph) and benzyl groups]. C-terminal modification primarily affected mu-opioid receptor affinities, which increased maximally 1700-fold relative to the prototype delta-antagonist H-Dmt-Tic-NH(2) and differentially modified bioactivity. In the absence of a spacer (1), the analogue exhibited dual delta-agonism (pEC(50), 7.28) and delta-antagonism (pA(2), 7.90). H-Dmt-Tic-NH-CH(2)-1H-benzimidazole-2-yl (Bid) (2) became a highly potent delta-agonist (pEC(50), 9.90), slightly greater than deltorphin C (pEC(50), 9.56), with mu-agonism (pE(50), 7.57), while H-Dmt-Tic-Gly-NH-CH(2)-Bid (4) retained potent delta-antagonism (pA(2), 9.0) but with an order of magnitude less mu-agonism. Similarly, H-Dmt-Tic-Gly-NH-Ph (5) had nearly equivalent high delta-agonism (pEC(50), 8.52) and mu-agonism (pEC(50), 8.59), while H-Dmt-Tic-Gly-NH-CH(2)-Ph (6) whose spacer was longer by a single methylene group exhibited potent delta-antagonism (pA(2), 9.25) and very high mu-agonism (pEC(50), 8.57). These data confirm that the distance between the Dmt-Tic pharmacophore and a third aromatic nucleus is an important criterion in converting Dmt-Tic from a highly potent delta-antagonist into a potent delta-agonist or into ligands with mixed delta- and mu-opioid properties.
Pharmacokinetic analysis of beta-aminopropionitrile in rabbits. (1996)

beta-Aminopropionitrile (beta APN), inhibits the activity of lysyl oxidase, an important enzyme for the post-translational formation of inter- and intramolecular covalent cross-linking between the connective tissue proteins, collagen and elastin. We became interested in the possible use of this compound as a therapeutic agent in the so-called human collagen diseases. beta APN's action mechanism is known, but its pharmacokinetics in rabbits have not yet been determined. The present study defined the kinetic parameters of beta APN in rabbits, after oral or intravenous (iv) administration. The HPLC technique was recently modified using OPA (ortho-phthalaldehyde) as the derivative agent. beta APN plasma concentration vs time following the iv administration of 200 mg/kg was best described by the biexponential equation C = 92.43.e(-0.0728 t) + 61.78.e(-0.0088 t) (t1/2 beta = 78.73 +/- 5.19 min; Vc = 1.29 +/- 0.04 L.kg-1). After oral administration, beta APN followed a zero-order absorption pattern (Ko = 3.02 +/- 0.34 mg.kg-1.min-1), which means that the beta APN reached the blood very quickly.