gebhart/patrepeval huggingface dataset:
The contributions of dsRNA structure to Dicer specificity and efficiency (2005)

Dicer processes long double-stranded RNA (dsRNA) and pre-microRNAs to generate the functional intermediates (short interfering RNAs and microRNAs) of the RNA interference pathway. Here we identify features of RNA structure that affect Dicer specificity and efficiency. The data presented show that various attributes of the 3' end structure, including overhang length and sequence composition, play a primary role in determining the position of Dicer cleavage in both dsRNA and unimolecular, short hairpin RNA (shRNA). We also demonstrate that siRNA end structure affects overall silencing functionality. Awareness of these new features of Dicer cleavage specificity as it is related to siRNA functionality provides a more detailed understanding of the RNAi mechanism and can shape the development of hairpins with enhanced functionality.
Approaches to improve engineered vaccines for human immunodeficiency virus and other viruses that cause chronic infections (1999)

We used several approaches to develop enhanced vaccines for chronic viral infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). 1) Selected epitopes were used to avoid potentially harmful immune responses. 2) Linkage between helper and cytotoxic T-lymphocyte (CTL) epitopes was found to be important. 3) We developed an "epitope enhancement" approach modifying the sequences of epitopes to make more potent vaccines, including examples for HIV and HCV epitopes presented by murine class II and human class I major histocompatibility complex (MHC) molecules. 4) CTL avidity was found to be important for clearing viral infections in vivo, and the mechanism was examined. High-avidity CTLs, however, were found to undergo apoptosis when confronted with high-density antigen, through a mechanism involving tumor necrosis factor (TNF), TNF-RII, and a permissive state induced through the T-cell receptor. 5) We employed cytokines in the adjuvant to steer immune responses toward desired phenotypes, and showed synergy between cytokines. 6) Intrarectal immunization with peptide vaccine induced mucosal and systemic CTL. Local mucosal CTL were found to be critical for resistance to mucosal viral transmission and this resistance was enhanced with mucosally delivered interleukin-12. 7) We used an asymmetry in induction of mucosal and systemic immune responses to circumvent pre-existing vaccinia immunity for use of recombinant vaccinia vaccines.
Induction of Humoral and CD8+ T Cell Responses Are Required for Protection against Lethal Ebola Virus Infection (2005)

Ebola virus (EBOV)-like particles (eVLP), composed of the EBOV glycoprotein and matrix viral protein (VP)40 with a lipid membrane, are a highly efficacious method of immunization against EBOV infection. The exact requirements for immunity against EBOV infection are poorly defined at this time. The goal of this work was to determine the requirements for EBOV immunity following eVLP vaccination. Vaccination of BALB/c or C57BL/6 mice with eVLPs in conjunction with QS-21 adjuvant resulted in mixed IgG subclass responses, a Th1-like memory cytokine response, and protection from lethal EBOV challenge. Further, this vaccination schedule led to the generation of both CD4(+) and CD8(+) IFN-gamma(+) T cells recognizing specific peptides within glycoprotein and VP40. The transfer of both serum and splenocytes, but not serum or splenocytes alone, from eVLP-vaccinated mice conferred protection against lethal EBOV infection in these studies. B cells were required for eVLP-mediated immunity to EBOV because B cell-deficient mice vaccinated with eVLPs were not protected from lethal EBOV challenge. We also found that CD8(+), but not CD4(+), T cells are absolutely required for eVLP-mediated protection against EBOV infection. Further, eVLP-induced protective mechanisms were perforin-independent, but IFN-gamma-dependent. Taken together, both EBOV-specific humoral and cytotoxic CD8(+) T cell responses are critical to mediate protection against filoviruses following eVLP vaccination.
Expression studies of catalytic antibodies. (1995)

We have examined the positive influence of human constant regions on the folding and bacterial expression of active soluble mouse immunoglobulin variable domains derived from a number of catalytic antibodies. Expression yields of eight hybridoma- and myeloma-derived chimeric Fab fragments are compared in both shake flasks and high density fermentations. In addition the usefulness of this system for the generation of in vivo expression libraries is examined by constructing and expressing combinations of heavy and light chain variable regions that were not selected as a pair during an immune response. A mutagenesis study of one of the recombinant catalytic Fab fragments reveals that single amino acid substitutions can have dramatic effects on the expression yield. This system should be generally applicable to the production of Fab fragments of catalytic and other hybridoma-derived antibodies for crystallographic and structure-function studies.
Immunology, Immunopathology, and Immunity (2001)

The sixth edition of this best-selling textbook presents a systematic account of the effects, both good and bad, of the immune system.
Special emphasis is placed on what the immune system actually does in causing and preventing disease. Divided into two parts, the sixth edition discusses inflammation, the fundamentals of the immune system and how it is activated, the seven immune effector mechanisms, and how these effector mechanisms act not only to protect against infection and cancer but also to cause diseases.
Valuable reading for physicians, medical students, graduate students, nurse practitioners, physician assistants, teachers of immunology, and advanced courses in immunology.
Electronic Only, 753 pages, illustrations, index.
Phenyl-substituted prostaglandins: potent and selective antiglaucoma agents (1993)

A series of phenyl-substituted analogues of prostaglandin F2 alpha (PGF2 alpha) were prepared and evaluated for ocular hypotensive effect and side effects in different animal models. In addition, the activity of the analogues on FP receptors was studied in vitro. The results were compared with those of PGF2 alpha and its isopropyl ester. The phenyl-substituted PGF2 alpha analogues exhibited good intraocular pressure reducing effect, were more selective, and exhibited a much higher therapeutic index in the eye than PGF2 alpha or its isopropyl ester. The analogues exhibited high activity on FP receptors in a stereoselective manner for the 15 alpha-hydroxyl group.
A dose‐ranging study of the efficacy and safety of tamsulosin, the first prostate‐selective &agr; 1A ‐adrenoceptor antagonist*, in patients with benign prostatic obstruction (1997)

Tamsulosin is well tolerated and effective in improving urinary flow and relieving LUTS associated with BPO. Optimal effects are achieved with tamsulosin 0.4 mg administered once daily.
Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms (2013)

These findings support the notion for clinical application of hMSCs and/or their secretory factors as a pharmacoregenerative modality for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic lung disorders.
Large‐Area Ordered Quantum‐Dot Monolayers via Phase Separation During Spin‐Casting (2005)

Abstract We investigate a new method for forming large‐area (&gt; cm 2 ) ordered monolayers of colloidal nanocrystal quantum dots (QDs). The QD thin films are formed in a single step by spin‐casting a mixed solution of aromatic organic materials and aliphatically capped QDs. The two different materials phase separate during solvent drying, and for a predefined set of conditions the QDs can assemble into hexagonally close‐packed crystalline domains. We demonstrate the robustness and flexibility of this phase‐separation process, as well as how the properties of the resulting films can be controlled in a precise and repeatable manner. Solution concentration, solvent ratio, QD size distribution, and QD aspect ratio affect the morphology of the cast thin‐film structure. Controlling all of these factors allows the creation of colloidal‐crystal domains that are square micrometers in size, containing tens of thousands of individual nanocrystals per grain. Such fabrication of large‐area, engineered layers of nanoscale materials brings the beneficial properties of inorganic QDs into the realm of nanotechnology. For example, this technique has already enabled significant improvements in the performance of QD light‐emitting devices.
Susceptibility of Plasmodium falciparum to a combination of thymidine and ICI D1694, a quinazoline antifolate directed at thymidylate synthase (1994)

Unlike mammalian cells, malarial parasites lack the enzymes to salvage preformed pyrimidines. For this reason, a combination of a thymidylate synthase inhibitor and the nucleoside thymidine should provide selective antimalarial activity even in the absence of any known active site differences between malarial and mammalian thymidylate synthases. To test this hypothesis, we evaluated the in vitro antimalarial activity of ICI D1694, a quinazoline antifolate that inhibits thymidylate synthase in mammalian cells. ICI D1694 inhibited the in vitro proliferation of Plasmodium falciparum with a 50% inhibitory concentration of 20 microM. As predicted, this antimalarial activity was not affected by the presence of 10 microM thymidine in the culture medium. In contrast, five different mammalian cells, several of which were susceptible to nanomolar levels of ICI D1694 in the absence of thymidine, were rescued by thymidine. At doses of 100 microM ICI D1694 and 10 microM thymidine, the proliferation of parasites was completely inhibited, but the proliferation of all mammalian cells remained unaffected. A test of susceptibility patterns among five different isolates of P. falciparum revealed that strains resistant to pyrimethamine, cycloguanil, or chloroquine had susceptibilities to ICI D1694 essentially the same as those of wild-type parasites. These findings are consistent with the hypothesis that, intracellularly, ICI D1694 inhibits P. falciparum thymidylate synthase. Overall, it is clear that even with an inhibitor of malarial thymidylate synthase that is not particularly effective in itself, one can obtain selective inhibition of parasites if the antimalarial agent is used in combination with thymidine. More effective inhibitors of malarial thymidylate synthase will undoubtedly lead to selective chemotherapy in vivo.
Molecular recognition in aqueous media. New binding studies provide further insights into the cation-.pi. interaction and related phenomena (1993)

We describe a large number of binding studies in aqueous media designed to provide new insights into noncovalent binding interactions, especially the cation-π interaction. The studies include 7 different hosts, over 70 guests, and over 150 new binding constants. In addition to the now standard NMR methods, circular dichroism has proven to be an especially useful tool for determining aqueous binding constants. We have found that, in addition to the alkyliminium and tetraalkylammonium guests we have studied previously, sulfonium and guanidinium guests also show substantial cation-π effects. Bromination of the host greatly enhances its binding ability in a general fashion, primarily as a result of hydrophobic interactions. Addition of methoxy groups did not enhance binding, apparently as a result of a collapse of the host into a conformation that is not suitable for binding. Replacement of two benzene rings of the host by furans or thiophenes also did not enhance binding. Ab initio calculations provide a rationalization for this effect and suggest a clearer model for the cation-π interaction.
H. pylori virulence factors (1998)

Among people infected with Helicobacter pylori, the virulence of the infecting strain is a major determinant of who develops disease. Strains producing vacuolating cytotoxin activity are more commonly isolated from people with peptic ulcers than without. The gene encoding the toxin, vacA, varies between strains, especially in its signal sequence and mid regions. vacA genotype influences cytotoxin activity, and signal sequence type correlates closely with peptic ulceration. Infection with strains possessing cagA (cytotoxin associated gene A) is more common among people with peptic ulceration or gastric adenocarcinoma than without. cagA is a marker for the cag pathogenicity island, which includes genes necessary for the enhanced inflammation induced by pathogenic strains. Serological detection of infection with cagA+ strains is at present the best practical test for virulence. However, before a strategy of screening and selective treatment can be considered, it is important to assess whether cagA- strains are entirely non-pathogenic.
High‐Resolution Molecular Validation of Self‐Renewal and Spontaneous Differentiation in Clinical‐Grade Adipose‐Tissue Derived Human Mesenchymal Stem Cells (2014)

Improving the effectiveness of adipose-tissue derived human mesenchymal stromal/stem cells (AMSCs) for skeletal therapies requires a detailed characterization of mechanisms supporting cell proliferation and multi-potency. We investigated the molecular phenotype of AMSCs that were either actively proliferating in platelet lysate or in a basal non-proliferative state. Flow cytometry combined with high-throughput RNA sequencing (RNASeq) and RT-qPCR analyses validate that AMSCs express classic mesenchymal cell surface markers (e.g., CD44, CD73/NT5E, CD90/THY1, and CD105/ENG). Expression of CD90 is selectively elevated at confluence. Self-renewing AMSCs express a standard cell cycle program that successively mediates DNA replication, chromatin packaging, cyto-architectural enlargement, and mitotic division. Confluent AMSCs preferentially express genes involved in extracellular matrix (ECM) formation and cellular communication. For example, cell cycle-related biomarkers (e.g., cyclins E2 and B2, transcription factor E2F1) and histone-related genes (e.g., H4, HINFP, NPAT) are elevated in proliferating AMSCs, while ECM genes are strongly upregulated (>10-fold) in quiescent AMSCs. AMSCs also express pluripotency genes (e.g., POU5F1, NANOG, KLF4) and early mesenchymal markers (e.g., NES, ACTA2) consistent with their multipotent phenotype. Strikingly, AMSCs modulate expression of WNT signaling components and switch production of WNT ligands (from WNT5A/WNT5B/WNT7B to WNT2/WNT2B), while upregulating WNT-related genes (WISP2, SFRP2, and SFRP4). Furthermore, post-proliferative AMSCs spontaneously express fibroblastic, osteogenic, chondrogenic, and adipogenic biomarkers when maintained in confluent cultures. Our findings validate the biological properties of self-renewing and multi-potent AMSCs by providing high-resolution quality control data that support their clinical versatility.
Passenger Transport Flows between European Member States and its Neighbouring Countries - Estimation Methodology for Air Transport (2007)

The objective of this paper is to forecast air passenger numbers between the European Union and its neighbouring countries. With the help of an intensive research, all international airlines and their destinations within the assessed countries have been identified in the paper. Based on flight schedules of 2006 and average load factors as well as specific aircraft types, a tool has been set up to calculate passenger numbers for 2006. Sub-tools have been developed for scheduled, charter, and low-cost airlines as they differ significantly in the mentioned parameters. The second part of the paper comprises a forecast scenario regarding passenger numbers in 2020. Based on the calibrated tool for 2006, growth rates for business and tourism have been used for forecasting air passenger numbers in 2020.
Radionuclide quantitation of left-to right cardiac shunts using deconvolution analysis: concise communication. (1981)

Quantitative radionuclide angiocardiography (QRAC) was performed with and without deconvolution analysis (DA) in 87 children with various heart disorders. QRAC shunt quantitation was possible without DA in 70% of the cases and with DA in 95%. Among 21 patients with prolonged bolus injections, quantitation of the shunt was possible in 52% of the cases without DA an in all cases with DA. Correlation between oximetry and QRAC with DA was better than between oximetry and QRAC without DA. It is concluded that QRAC with DA is a more reliable, noninvasive means for detection and quantitation of left-to-right cardiac shunts than QRAC without DA.
Complex regional pain syndrome: a review. (2005)

Complex regional pain syndrome (CRPS) is a challenging neuropathic pain state, quite difficult to comprehend and treat. Its pathophysiological mechanisms are unclear and its treatment is difficult. Multiple factors play a role in the generation and maintenance of CRPS. A close interdisciplinary collaboration amongst the psychologist, physical and occupational therapists, neurologist and pain medicine consultants is necessary to achieve optimal treatment effects. The primary goals of managing patients with this syndrome are to: 1) perform a comprehensive diagnostic evaluation, 2) be prompt and aggressive in treatment interventions, 3) assess and reassess the patient's clinical and psychological status, 4) be consistently supportive, and 5) strive for the maximal amount of pain relief and functional improvement. This article reviews the different aspects of CRPS including definition, classification, epidemiology and natural history, clinical presentation, pathophysiology and management.
Suppression of nonspecific binding of avidin-biotin complex (ABC) to proteins electroblotted to nitrocellulose paper. (1986)

Nitrocellulose blots of cell extracts reacted in sequence with biotinylated lectins and horseradish peroxidase-labeled avidin-biotin complex (ABC) often show considerable nonspecific staining of protein bands. Experiments were performed to determine which of the components of the ABC were responsible for this and whether or not the nature and ionic strength of the buffer used could alter this binding. Furthermore, as powdered non-fat milk has been proposed as a possible blocking agent for nonspecific binding of ABC, we sought to determine if it would adequately block that binding in our system. The initial experiments showed that nonspecific binding of ABC to proteins transferred to nitrocellulose membranes was due to the avidin component of the ABC; little, if any, binding was seen if biotin alone was incubated with these blots. The spurious binding was shown to be primarily due to the high affinity of avidin to proteins electroblotted to nitrocellulose, when incubated in low-salt buffers. Low-fat milk added to the buffer reduced overall nonspecific reactivity but produced additional artifacts in the form of bands that were not seen in other preparations. Nonspecific avidin binding to proteins transferred to nitrocellulose can therefore be effectively reduced by adding extra salt to buffers, whereas the addition of non-fat dry milk does not seem suitable for this purpose.
ANTI-CD3 F(abʼ)2 FRAGMENTS ARE IMMUNOSUPPRESSIVE IN VIVO WITHOUT EVOKING EITHER THE STRONG HUMORAL RESPONSE OR MORBIDITY ASSOCIATED WITH WHOLE mAb (1990)

The use of anti-CD3 monoclonal antibodies to treat organ allograft rejection has been complicated by (1) the morbidity associated with the initial dose, (2) the humoral response of the patients against the mAbs, and (3) the generalized immunosuppression induced by the mAbs. We investigated the potential of F(ab')2 fragments of the anti-murine-CD3 mAb, 145-2C11, to avoid these complications in the murine model. Both whole mAb and F(ab')2 fragments induced T cell depletion. However, injection of F(ab')2 fragments of anti-CD3 mAb did not cause T cell activation, and did not induce the morbidity and mortality observed following injection of whole mAb. The humoral response against the F(ab')2 fragments was significantly reduced compared with the response against the whole mAb. Furthermore, repeated administration of F(ab')2 fragments of anti-CD3 mAb resulted in prolongation of allogeneic skin graft survival superior to that seen following treatment with a single dose of whole mAb. Finally, while T cells from mice treated with whole mAb displayed profound suppression of in vitro CTL generation, T cells from mice treated with F(ab')2 fragments had significant in vitro CTL function. These results suggest that the use of F(ab')2 fragments of anti-CD3 mAb may offer significant advantages over whole mAb for the induction and maintenance of immunosuppression.
Halide transport in Xenopus oocytes. (1991)

1. Radioisotopes and intracellular microelectrodes were used to characterize the permeability of Xenopus oocytes to chloride and other halides. 2. Uptake of 36Cl had a half-time for equilibration of approximately 3 h, with an initial rate of Cl- entry corresponding to a permeability coefficient of 3.9 x 10(-7) cm/s, and an equilibrium uptake of 36Cl of 33 mM. 3. Replacement of bathing Na+ by K+ depolarized the oocytes from -46 to -7 mV and stimulated influx approximately 3-fold. 4. Influx was linearly dependent on bathing [Cl-] and was temperature dependent with an activation energy of 46 kJ/mol. Influx of 125I of 36Cl was not affected by the presence of equal concentrations of other halides or thiocyanate. These results are consistent with a channel-mediated entry mechanism. 5. Diphenylamine-2-carboxylate (DPAC) and 9-anthracene carboxylate (9-AC), blockers of Cl- channels in other cells, inhibited Cl- entry with dissociation constants (Kds) of approximately 5 x 10(-4) and approximately 10(-3) M, respectively. Inhibitors of Cl(-)-HCO3- exchange or Na(+)-K(+)-2Cl- co-transport did not affect Cl- influx. 6. Attempts to lower or raise intracellular Ca2+ with BAPTA or A23187, respectively, were also without effect on Cl- influx. 7. The halide selectivity sequence determined with isotopes was I- (3.2) greater than Br- (1.3) greater than Cl- (1.0). However, DPAC inhibited almost all of the 36Cl influx but only a small fraction of 125I influx. 8. Replacement of bathing Cl- by I- or Br-resulted in hyperpolarizations, from which the same selectivity sequence was determined. 9. Replacement of bathing Cl- by gluconate caused a marked depolarization, which was inhibited by DPAC and, less potently, by 9-AC.
Degradable Conjugated Polymers: Synthesis and Applications in Enrichment of Semiconducting Single‐Walled Carbon Nanotubes (2011)

Abstract Polymers which enrich semiconducting single‐walled carbon nanotubes (SWNTs) and are also removable after enrichment are highly desirable for achieving high‐performance field‐effect transistors (FETs). We have designed and synthesized a new class of alternating copolymers containing main‐chain fluorene and hydrofluoric acid (HF) degradable disilane for sorting and preferentially suspending semiconducting nanotube species. The results of optical absorbance, photoluminescence emission, and resonant Raman scattering show that poly[(9,9‐dioctylfluorenyl‐2,7‐diyl)‐alt‐co‐1,1,2,2‐tetramethyl‐disilane] preferentially suspends semiconducting nanotubes with larger chiral angle (25°–28°) and larger diameter (1.03 nm–1.17 nm) (specifically (8,7), (9,7) and (9,8) species) present in HiPCO nanotube samples. Computer simulation shows that P1 preferentially interacts with (8,7) (semiconducting) over (7,7) (metallic) species, confirming that P1 selects larger diameter, larger chiral angle semiconducting tubes. P1 wrapped on the surface of SWNTs is easily washed off through degradation of the disilane bond of the alternating polymer main chain in HF, yielding “clean” purified SWNTs. We have applied the semiconducting species enriched SWNTs to prepare solution‐processed FET devices with random nanotube network active channels. The devices exhibit stable p‐type semiconductor behavior in air with very promising characteristics. The on/off current ratio reaches up to 15 000, with on‐current level of around 10 μA and estimated hole mobility of 5.2 cm 2 V −1 s −1 .