gebhart/patrepeval huggingface dataset:
Abnormal Priming of CD4+T Cells by Dendritic Cells Expressing Hepatitis C Virus Core and E1 Proteins (2002)

Patients infected with hepatitis C virus (HCV) have an impaired response against HCV antigens while keeping immune competence for other antigens. We hypothesized that expression of HCV proteins in infected dendritic cells (DC) might impair their antigen-presenting function, leading to a defective anti-HCV T-cell immunity. To test this hypothesis, DC from normal donors were transduced with an adenovirus coding for HCV core and E1 proteins and these cells (DC-CE1) were used to stimulate T lymphocytes. DC-CE1 were poor stimulators of allogeneic reactions and of autologous primary and secondary proliferative responses. Autologous T cells stimulated with DC-CE1 exhibited a pattern of incomplete activation characterized by enhanced CD25 expression but reduced interleukin 2 production. The same pattern of incomplete lymphocyte activation was observed in CD4(+) T cells responding to HCV core in patients with chronic HCV infection. However, CD4(+) response to HCV core was normal in patients who cleared HCV after alpha interferon therapy. Moreover, a normal CD4(+) response to tetanus toxoid was found in both chronic HCV carriers and patients who had eliminated the infection. Our results suggest that expression of HCV structural antigens in infected DC disturbs their antigen-presenting function, leading to incomplete activation of anti-HCV-specific T cells and chronicity of infection. However, presentation of unrelated antigens by noninfected DC would allow normal T-cell immunity to other pathogens.
Wheat dwarf virus Ac/Ds vectors: expression and excision of transposable elements introduced into various cereals by a viral replicon. (1990)

The maize transposon Activator (Ac) and in vitro-generated nonautonomous derivatives thereof [Ac delta or Dissociation (Ds) elements] were inserted into the genome of a geminivirus of graminaceous plants, wheat dwarf virus, at a site that does not interfere with viral replication. These recombinant viral genomes were introduced into wheat, maize, and rice protoplasts, where rapid and efficient excision of Ac was observed. Excision was detected only in vectors in which, after transfection, the virus could replicate. This result is not restricted to the autonomous Ac; excision of Ds elements was also induced by transposase activity provided in trans by plasmids expressing the cDNA of Ac. The potential of this combination of a transposon with a viral replicon for plant molecular genetic engineering is discussed.
Quantum Mechanics Helps in Searching for a Needle in a Haystack (1997)

Quantum mechanics can speed up a range of search applications over unsorted data. For example, imagine a phone directory containing $N$ names arranged in completely random order. To find someone's phone number with a probability of 50%, any classical algorithm (whether deterministic or probabilistic) will need to access the database a minimum of $0.5N$ times. Quantum mechanical systems can be in a superposition of states and simultaneously examine multiple names. By properly adjusting the phases of various operations, successful computations reinforce each other while others interfere randomly. As a result, the desired phone number can be obtained in only $O(\sqrt{N})$ accesses to the database.
Small RNAs Correspond to Centromere Heterochromatic Repeats (2002)

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Homo‐ and Heteropentanuclear Coordination Compounds with Td Symmetry – the Solid State Structures of [MZn4(L)4(L′)6] (M = CoII or Zn; L = chloride or acac; L′ = 1,2,3‐benzotriazolate) (2008)

Abstract The syntheses of homo‐ and heteropentanuclear coordination compounds with the molecular formulae [MZn 4 (L) 4 (L′) 6 ] (M = Co II or Zn; L = chloride or acac; L′ = 1,2,3‐benzotriazolate) are reported. These compounds display a highly symmetric coordination unit consisting of a central metal ion (M = Co II or Zn) which is octahedrally coordinated by 6 tridentate benzotriazolate‐type ligands via their N(2) donor atom. The benzotriazolate ligands span the edges of an imaginary tetrahedron thus providing four coordination sites at the corners of the tetrahedron, which are then filled by four zinc ions. The coordination shell of the latter are completed by bidentate acetylacetonate (acac) ligands or by chloride anions, respectively. The solid state structures of two homopentanuclear metal complexes, namely [Zn 5 (acac) 4 (bta) 6 ]·4C 6 H 12 ( 1 ) (acacH = acetylacetone; btaH = 1,2,3‐benzotriazole), and [Zn 5 Cl 4 (Me 2 bta) 6 ]·2DMF ( 2 ) (Me 2 btaH = 5,6‐dimethyl‐1,2,3‐benzotriazole) were determined by single crystal X‐ray structure analysis. The heteropentanuclear metal complex [Co II Zn 4 Cl 4 (Me 2 bta) 6 ]·2DMF ( 3 ) is isostructural with compound 2 . Compound 1 was synthesized from stoichiometric amounts of Zn(acac) 2 and btaH employing dichloromethane as solvent. The synthesis of compound 2 requires addition of an auxiliary base to the DMF solution of anhydrous ZnCl 2 and Me 2 btaH. For compound 3 a stoichiometric ratio of Co(NO 3 ) 2 ·6H 2 O, anhydrous ZnCl 2 and Me 2 btaH was employed during synthesis. Phase purity of all compounds was proved by X‐ray powder diffraction (XRPD) analysis, IR spectroscopy, and elemental analysis. Crystal data: for 1 (C 80 H 100 N 18 O 8 Zn 5 ): monoclinic, space group P 2 1 / c with a = 23.781(5) Å, b = 16.000(3) Å, c = 25.170(5) Å, β = 115.29(3)°, V = 8659(3) Å 3 , Z = 4, ρ = 1.357 g cm −3 . For 2 (C 54 H 62 Cl 4 N 20 O 2 Zn 5 ): cubic, space group $Fd{\bar 3}m$ with a = 23.367(3) Å, V = 12759(3) Å 3 , Z = 8, ρ = 1.553 g cm −3 . For 3 (C 54 H 62 Cl 4 CoN 20 O 2 Zn 4 ): cubic, space group $Fd{\bar 3}m$ with a = 23.443(3) Å, V = 12884(3) Å 3 , Z = 8, ρ = 1.532 g cm −3 .
Viral vectors : gene therapy and neuroscience applications (1995)

J.C. Glorioso, M.A. Bender, W. F Goins, D.J. Fink, and N. DeLuca, Herpes Simplex Virus as a Gene Delivery Vector for the Central Nervous System. A.D. Kwong and N. Frankel, Biology of Herpes Simplex Virus (HSV) Defective Viruses and Development of the Amplicon System. T Shenk Group C Adenoviruses as Vectors for Gene Therapy. J.S. Bartlett and R.J. Samulski, Genetics and Biology of Adeno-Associated Virus. R. Bannerji, Genetics and Biology of Retroviral Vectors. M.J. During, HSV Vectors in the Mammalian Brain: Molecular Analysis of Neuronal Physiology, Generation of Genetic Models, and Gene Therapy of Neurological Disorders. H.J. Federoff, The Use of Defective Herpes Simplex Virus Amplicon Vectors to Modify Neural Cells and the Nervous System. J. Verhaagen, W.T.J.M.C. Hermens, A.J.G.D. Holmaat, A.B. Oestreicher, and M. G. Kaplitt, Viral Vector-Mediated Gene Transfer in the Nervous System: Application to the Reconstruction of Neural Circuits in the Injured Mammalian Brain. D. Y Hol M.S. Lawrence, TJ. Meier, S.L Fink, and R. Dash, The Use of Herpes Simplex Virus Vectors for Protection from Necrotic Neuron Death. J. Yin, M. G. Kaplitt, and D. W. Pfaff, In Vivo Promoter Analysis in the Adult Central Nervous System Using Viral Vectors. B.L. Davidson and B.J. Roessler, Adenoviral Mediated Gene Transfer: Potential Therapeutic Applications. M. G. Kaplitt and M.J. During, Transfer and Expression of Potentially Therapeutic Genes into the Mammalian Central Nervous System in Vivo Using Adeno-Associated Viral Vectors. U.J. Kang, Genetic Modification of Cells with Retrovirus Vector for Grafting into the Central Nervous System. M.X. Wei, T Tamiya, X.O. Breakefield and E.A. Chiocca, Virus Vector-Mediated Transfer of Drug-Sensitivity Genes for Experimental BrainTumour Therapy. W. Hunter, S. Rabkin, and R. Martuza, Brain Tumour Therapy Using Genetically Engineered Replication-Competent Virus. M.R. Rosenfeld, J.J. Vershuuren, and J. Dalmau, Transfer and Expression of Antioncogenes and Paraneoplastic Genes in Normal and Neoplastic Cells in Vitro and in Vivo. G. Ugolini, Transneuronal Tracing with Alphaherpesviruses: A Review of the Methodology. J.P Card, Pseudorabies Virus Replication and Assembly in the Rodent Central Nervous System. A.D. Loewy, Pseudorabies Virus: A Transneuronal Tracer for Neuroanatomical Studies. T C. Mettenleiter, Molecular Properties of Alphaherpesviruses Used in Transneuronal Pathway Tracing. P. Coulon and A. Flamand, Molecular Analysis of Rabies and Pseudorabies Neurotropism. K. W. McDermott and M.B. Luskin, The Use of Retroviral Vectors in the Study of Cell Lineage and Migration during the Development of the Mammalian Central Nervous System. E.J. Snyder, Retroviral Vectors for the Study of Neuroembryology: Immortalisation of Neural Cells. References. Index.
Novobiocin:  Redesigning a DNA Gyrase Inhibitor for Selective Inhibition of Hsp90 (2006)

Novobiocin is a member of the coumermycin family of antibiotics and is a well-established inhibitor of DNA gyrase. Recent studies have shown that novobiocin binds to a previously unrecognized ATP-binding site at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at approximately 700 microM. In an effort to develop more efficacious inhibitors of the C-terminal binding site, a library of novobiocin analogues was prepared and initial structure-activity relationships revealed. These data suggested that the 4-hydroxy moiety of the coumarin ring and the 3'-carbamate of the noviose appendage were detrimental to Hsp90 inhibitory activity. In an effort to confirm these findings, 4-deshydroxy novobiocin (DHN1) and 3'-descarbamoyl-4-deshydroxynovobiocin (DHN2) were prepared and evaluated against Hsp90. Both compounds were significantly more potent than the natural product, and DHN2 proved to be more active than DHN1. In an effort to determine whether these moieties are important for DNA gyrase inhibition, these compounds were tested for their ability to inhibit DNA gyrase and found to exhibit significant reduction in gyrase activity. Thus, we have established the first set of compounds that clearly differentiate between the C-terminus of Hsp90 and DNA gyrase, converted a well-established gyrase inhibitor into a selective Hsp90 inhibitor, and confirmed essential structure-activity relationships for the coumermycin family of antibiotics.
GRAFT-VERSUS-HOST DISEASE (1968)

Graft-versus-host disease was induced in adult hybrid rats by injection of spleen cells from either or both parental strains. Under the conditions of these experiments, GVH disease infiltrates appeared in the hepatic portal areas in all rats splenectomized before injection, but rarely in intact or sham-operated animals. Although other explanations are possible, it is likely that removal of the splenic sites of lymphocyte fixation (3) allowed more opportunity for the injected parental cells to settle in the liver.
Immunoliposome targeting to murine CD4+ leucocytes is dependent on immune status. (1994)

Immunoliposomes were prepared from dipalmitoylphosphatidylcholine, dimyristoylphosphatidylglycerol, biotinylated PE, and surface-linked avidin-biotinylated GK1.5 monoclonal rat (anti-mouse CD4) IgG or F(ab)2. Anti-CD4 immunoliposomes bound quantitatively to CD4+ PBMC's in vitro. Intravenous injection of mice with 1 mumol anti-CD4 immunoliposomes resulted in targeting to a significant proportion (> 75%) of CD4+ PBMCs. Repeated administration of anti-CD4 immunoliposomes induced significant levels of anti-GK 1.5 IgG Ab, with concomitant reductions in immunoliposome plasma t1/2 and targeting efficacy, and increased volumes of distribution. The immunogenicity of the immunoliposome was enhanced if GK1.5 F(ab)2 instead of IgG was used as the targeting ligand. Lipophilic poly(ethylene glycol) derivatives incorporated into the immunoliposomes did not affect targeting efficiency but significantly enhanced immunogenicity. These results demonstrate that IgG or F(ab)2 immunoliposomes are highly immunogenic and that targeting in vivo is conditional on the immune status of the host.
Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells (2008)

The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-alpha in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-alpha. Further study indicated that IFN-gamma+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.
Development of novel analytical tools for complex carbohydrates (2004)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004.
Recombinant AAV as a Platform for Translating the Therapeutic Potential of RNA Interference (2013)

RNA interference has become a ubiquitous biological tool, and is being harnessed for therapeutic purposes as well. Therapeutic posttranscriptional gene silencing takes advantage of the endogenous RNAi pathway through delivery of either chemically synthesized siRNAs, or transgenes expressing hairpin-based inhibitory RNAs (e.g., shRNAs and artificial miRNAs). RNAi has expanded the field of viral gene therapy from gene replacement to gene knockdown. Here, we review various noncoding RNAs such as shRNAs, miRNAs, and miRNA decoys which can be utilized for therapeutic applications when expressed from recombinant adeno-associated vectors (AAV), and present examples of their basic design. In addition the basis of exploiting cellular miRNA profiles for detargeting AAV expression from specific cells is described. Finally, an overview of AAV-mediated RNAi preclinical studies is presented, and current RNAi-based clinical trials are reviewed.
New Antimicrobial Agents in Respiratory Medicine (2006)

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Splenic T lymphocytes die preferentially during heat-induced apoptosis: NuMA reorganization as a marker (1998)

We are investigating nuclear events during apoptosis in mouse splenic lymphocytes cultured immediately after isolation (controls) or after heat treatment (42 degreesC, 30 minutes), and have found that hyperthermia increased the level of apoptosis to double that of spontaneous apoptosis in controls within 6 hours. Immunolabelling for Nuclear Mitotic Apparatus Protein (NuMA) suggested that splenocytes were responding heterogeneously to the heat treatment. Whereas all nuclei in controls and about half of nuclei in heat-treated samples showed the usual diffuse nucleoplasmic labelling, 40-60% of nuclei in heated samples also contained numerous bright spots. We then examined whether the heterogeneity in NuMA organization might be an indication of a differential response of B and T lymphocytes to hyperthermia, and whether the presence of NuMA spots is related to the apoptotic process. NuMA labelling of heated fractionated splenocyte populations showed that 90% of nuclei in T-enriched cultures (less than or equal to 4% IgG+ cells), but only 25% of nuclei in B-enriched samples (less than or equal to 80% IgG+ cells), contained spots. As well, 2 hours after heat treatment of unfractionated cultures, greater than or equal to 90% of nuclei that were accumulating DNA strand breaks, as detected by TUNEL, exhibited NuMA spots. These data indicate that cells with NuMA spots are targetted for, or have initiated, the death program. Since most T cells, but few or no B cells, were spotty after heating, we conclude further that hyperthermia induces apoptosis preferentially in splenic T lymphocytes. The observation that the proportion of T cells was, on average, threefold greater in control than in heated samples after 24 hours in culture reinforces this conclusion.
Comparison of the heparanase enzymes from mouse melanoma cells, mouse macrophages, and human platelets (1996)

The intracellular heparanases from mouse macrophage and melanoma cells are very similar in terms of their size (60-80 kDa), pI (5.3-4.1), pH optimum (< or = 5.5), and interactions with heparin. These proteins are therefore likely to be identical, suggesting that tumour and blood cells utilise the same heparanase enzyme. The human platelet enzyme is similar to the mouse enzymes in terms of pH optimum (< or = 5.5) and pI value (5.3-4.8), but appears to be smaller in size (40-60 kDa). It also seems to differ from the mouse enzymes in aspects of its surface charge, and in its interactions with heparin. There was no indication that proteolysis was of significance for the enzymes, nor that they contained any sialic acid residues.
Detection of herpes simplex virus by 8 h in shell vial cultures with primary rabbit kidney cells (1989)

Shell vial (SV) cultures for herpes simplex virus using primary rabbit kidney cells stained at 8 h after inoculation were compared with 20-h SV cultures as well as conventional tissue culture. Of the 326 clinical specimens examined, conventional culture detected 67, and of these, 61 (91%) and 42 (63%) were detected by 20-h SV cultures and 8-h SV cultures, respectively.
Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning (2010)

Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals.
Ionizing radiation‐induced long‐term expression of senescence markers in mice is independent of p53 and immune status (2010)

Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized that IR-induced senescence markers could persist long-term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16(INK4a) expression, two hallmarks of cellular senescence and aging. BrdU-labeling experiments revealed that IR-induced damaged cells are preferentially eliminated, at least partially, in a tissue-dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild-type and Rag2(-/-) gammaC(-/-) mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long-term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors.
Modification by oxygen free radical scavengers of the metabolic and cardiovascular effects of endotoxin infusion in conscious rats. (1986)

Since oxygen free radicals may have a role in the pathophysiology of endotoxin shock, we have studied the effects of a wide range of compounds (alpha-tocopherol, reduced glutathione, allopurinol, superoxide dismutase (alone or in combination with catalase) and phenyl butylnitrone) that can act either to remove free radicals as they are generated or to prevent their generation. The effects of these substances on the metabolic and cardiovascular responses to endotoxin were examined in conscious rats. The intravenous infusion of endotoxin (10 mg/kg i.v. given over 4 h) resulted in systemic hypotension, transient tachycardia, an increase in plasma lactate, and an initial hyperglycemia followed, in those rats that died before 24 h, by hypoglycemia. The hypotension and tachycardia produced by endotoxin were not significantly modified by alpha-tocopherol, allopurinol, or superoxide dismutase, alone or in combination with catalase. The tachycardia was attenuated by reduced glutathione and phenyl butylnitrone. alpha-Tocopherol attenuated the initial hyperglycemia produced by endotoxin whilst alpha-tocopherol, allopurinol, and phenyl butylnitrone all significantly attenuated the endotoxin-induced increase in plasma lactate. Among the free radical scavenging systems studied, only alpha-tocopherol and phenyl butylnitrone improved survival. These results suggest a contribution from oxygen-free radicals to the pathophysiology of endotoxemia.
Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage (2005)

Intestinal glucagon-like peptide-1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9-39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state.