gebhart/patrepeval huggingface dataset:
A novel 165-base-pair terminal repeat sequence is the sole cis requirement for the adeno-associated virus life cycle (1997)

Adeno-associated virus (AAV) replication is dependent on two copies of a 145-bp inverted terminal repeat (ITR) that flank the AAV genome. This is the primary cis-acting element required for productive infection and the generation of recombinant AAV (rAAV) vectors. We have engineered a plasmid (pDD-2) containing only 165 bp of AAV sequence: two copies of the D element, a unique sequence adjacent to the AAV nicking site, flanking a single ITR. When assayed in vivo, this modified hairpin was sufficient for the replication of the plasmid vector when Rep and adenovirus (Ad) helper functions were supplied in trans. pDD-2 replication intermediates were characteristic of the AAV replication scheme in which linear monomer, dimer, and other higher-molecular-weight replicative intermediates are generated. Compared to infectious AAV clones for replication, the modified hairpin vector replicated more efficiently independent of size. Further analysis demonstrated conversion of the input circular plasmid to a linear substrate with AAV terminal repeat elements at either end as an initial step for replication. This conversion was independent of both Rep and Ad helper genes, suggesting the role of host factors in the production of these molecules. The generation of these substrates suggested resolution of the modified terminal repeat through a Holliday-like structure rather than replication as a mechanism for rescue. Production of replicative intermediates via this plasmid substrate were competent not only for AAV DNA replication but also for encapsidation, infection, integration, and subsequent rescue from the chromosome when superinfected with Ad and wild-type AAV. These studies demonstrate that this novel 165-bp ITR substrate is sufficient in cis for the AAV life cycle and should provide a valuable reagent for further dissecting the cis sequences involved in AAV replication, packaging, and integration. In addition, this novel plasmid vector can be used as a substrate for both rAAV vector production and synthetic plasmid vector delivery.
Functional characterization and biomarker identification in the Brown Norway model of allergic airway inflammation (2002)

1. The antigen-induced inflammatory response in the Brown Norway rat is a model commonly used to assess the impact of novel compounds on airway eosinophilia. A detailed functional, cellular and molecular characterization of this model has not yet been performed within a single study. This information together with the temporal changes in this phenomenon should be known before this model can be used, with confidence, to elucidate the mechanisms of action of novel anti-inflammatory drugs. 2. Antigen challenge caused an accumulation of eosinophils in lung tissue 24 h after challenge. Accumulation of CD2(+) T cells was not apparent until after 72 h. 3. Interestingly, mRNA for the Th2 type cytokines interleukin (IL)-4, IL-5 and IL-13 and eotaxin were elevated in lung tissue after challenge and the expression of IL-13 and eotaxin protein increased at around 8-12 h. The temporal changes in both the biomarker production and the functional responses are important factors to consider in protocol design prior to initiating a compound screening program. 4. A neutralising antibody (R73) against alphabeta-TCR caused a significant reduction in T cell numbers accompanied by a significant suppression of eosinophil accumulation. 5. Airway hyperreactivity (AHR) was not apparent in this specific Brown Norway model in sensitized animals after a single or multiple challenges although eosinophil influx was seen in the same animals. 6. In conclusion, this is a convenient pre-clinical model (incorporating the measurement of biomarkers and functional responses) for screening novel small molecule inhibitors and/or biotherapeutics targeted against T cell/eosinophil infiltration/activation.
Genetic incompatibility combined with female-lethality is effective and robust in simulations of Aedes aegypti population control (2018)

Recent reports of CRISPR/Cas9-based suppression gene drives in insects underscore the challenge of overcoming genetic resistance. Here we present results from agent-based simulation modeling of a novel Field-Amplified Male Sterility System (FAMSS) that outperforms suppression gene drives when challenged with genetic resistance. FAMSS combines a recently described synthetic genetic incompatibility approach with previously demonstrated female-lethality constructs. Our results suggest that FAMSS will be an effective strategy for temporally and spatially self-limited suppression of the disease vectoring mosquito, Aedes aegypti .
Quantum Theory of Chemical Reaction Dynamics (1998)

It is now possible to use rigorous quantum scattering theory to perform accurate calculations on the detailed state-to-state dynamics of chemical reactions in the gas phase. Calculations on simple reactions, such as H + D2 --> HD + D and F + H2 --> HF + H, compete with experiment in their accuracy. Recent advances in theory promise to extend such accurate predictions to more complicated reactions, such as OH + H2 --> H2O + H, and even to reactions of molecules on solid surfaces. New experimental techniques for probing reaction transition states, such as negative-ion photodetachment spectroscopy and pump-probe femtosecond spectroscopy, are stimulating the development of new theories.
United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants (1991)

Thirteen centers participated in a multicenter database with systematic evaluation of US and Canadian patients who had adrenal medullary transplantation for Parkinson's disease. This voluntary registry collected demographic, safety, and efficacy data using the same scoring measures over a 2-year follow-up period. Baseline data on 61 patients and 2-year follow-up data on 56 patients were compared. Eighteen percent died during the study period, and one-half of these deaths were related or questionably related to the surgery. Of the remaining 45 patients with data, global improvement, defined as an improved summed score of the "on" and "off" motor and activities of daily living functions from the Unified Parkinson's Disease Rating Scale, occurred in 32% of the patients at 2 years after surgery. At follow-up, significant group improvement persisted in the amount of daily "on" time and the quality of "off" function, but other measures were no better than baseline. When the global improvement calculation was based on the total sample and included deaths and patients lost to follow-up as "not improved," only 19% were improved 2 years after surgery. Twenty-two percent of survivors had persistent psychiatric morbidity not present prior to surgery. These data document a modest group improvement in "off" function after neurotransplantation, but a serious level of mortality and morbidity.
Minimally invasive colectomy (1993)

Laparoscopic surgical techniques have recently been applied to various types of colon resection. Early reports have focused on the technical feasibility of these procedures, and it has not yet been clearly shown that such procedures benefit the patient. We reviewed our experience with 28 attempted minimally invasive colectomies (MICs) performed over a nine-month period. Laparoscopic or laparoscopic-assisted resections were successfully completed in 24 of these patients. We compared the results of surgery in these 24 patients with a group of 33 patients undergoing similar procedures at the same institution by the same surgeon in the nine months preceding the laparoscopic experience. The two groups of patients were similar with respect to age, weight, and the types of procedures performed. However, the postoperative length of stay for patients undergoing MIC (4.8 days) was significantly shorter than for those undergoing open colectomies (8.2 days). Patients undergoing MIC also regained bowel function significantly earlier than those undergoing open colectomy. The operative times for the minimally invasive procedures were significantly longer than for those undergoing open colectomy. No surgically related deaths were encountered, and morbidity was 13 percent. None of the four patients converted from laparoscopic to open colectomy suffered complications as a result of the attempted laparoscopic procedure. We conclude that MIC can be safely performed and does appear to reduce the duration of postoperative ileus and decrease the length of postoperative hospitalization.
The XRCC2 DNA repair gene from human and mouse encodes a novel member of the recA/RAD51 family (1998)

We recently identified a positional candidate for the XRCC2 DNA repair gene at human chromosome 7q36.1. We have now cloned the cDNA for this gene from both human and mouse and show that it is a highly conserved novel member of the recA / RAD51 recombination repair gene family. The cDNA is able to complement significantly the phenotype of a unique cell line, irs1 , which shows extreme sensitivity to DNA cross-linking agents and genetic instability. Thisphenotype is consistent with a role for the XRCC2 gene in recombination repair in somatic cells, suggesting that in addition to RAD51 , other members of this gene family have an important function in high fidelity repair processes in mammals. Despite this function, the XRCC2 gene transcript is expressed at a very low level in somatic tissue, but is elevated in mouse testis, suggesting an additional role in meiosis.
Genome Sequence and Comparative Analysis of the Solvent-Producing BacteriumClostridium acetobutylicum (2001)

The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria.
Improved Polymerase Chain Reaction Detection of Clonal T-Cell Lymphoid Neoplasms (1995)

We have developed and tested a rapid and sensitive method of detecting expansion of T-cell clones using the polymerase chain reaction (PCR) and a single set of consensus primers for the V and J regions to amplify rearranged T-cell receptor-gamma (TCR-gamma) genes. Monoclonality was continued in all of the 18 cases of T-cell neoplasms tested, but not in reactive lymphadenopathy, non-Hodgkin's B lymphomas, and Hodgkin's disease. PCR analysis, using the primer sequence outlined in this study, had an overall specificity of 100% when compared with Southern blot analysis. No false-negative results were observed, certainly owing to the choice of consensus primers and to the control of PCR reactions on agarose gels before testing for clonality by separation of PCR products on polyacrylamide gels. This method for the detection of T-cell monoclonality can be especially useful in cases that are diagnostically problematic with standard histological and immunological analysis and in cases where the material available is limited.
Wounding Induces the Rapid and Transient Activation of a Specific MAP Kinase Pathway (1997)

, Wilco Ligterink, Irute Meskiene, Patrick J. Barker, Erwin Heberle-Bors, Neville S. Huskisson, Heribert Hirt, Wounding Induces the Rapid and Transient Activation of a Specific MAP Kinase Pathway, The Plant Cell, Vol. 9, No. 1 (Jan., 1997), pp. 75-83
DDQ-promoted dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones by a radical ion mechanism (2011)

A novel and facile DDQ-mediated dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones is described. The formation of lactones proceeds by a radical ion mechanism, which has been established by DPPH˙-mediated chemical identification, ESR spectroscopy and an enol intermediate trapping.
Implications of Repeated Trinexapac‐Ethyl Applications on Kentucky Bluegrass (2001)

Reducing turfgrass clipping production is often the goal of managers who recognize the need to save time, money, or landfill space. The objective of this study was to investigate the long‐term implications of repeated trinexapac‐ethyl [4‐(cyclopropyl‐α‐hydroxy‐methylene)‐3, 5‐dioxocyclohexanecarboxylic acid ethyl ester] applications at two fertility levels (150 and 300 kg N ha −1 yr −1 ) on Kentucky bluegrass ( Poa pratensis L.). Trinexapac‐ethyl (TE) was applied at 0.17, 0.23, or 0.29 kg a.i. ha −1 every 4 wk or at 0.23, 0.29, or 0.34 kg a.i. ha −1 every 6 wk for three growing seasons. Clippings were reduced by 22 to 41% when TE was applied every 4 wk (five applications per season) from May through August, and turfgrass quality was improved. A 6‐wk application schedule (four applications per season) did not reduce clipping production as consistently as the 4‐wk application schedule due to a postsuppression rebound effect Nitrogen fertility above 150 kg N ha −1 yr −1 was not necessary to maintain excellent turfgrass quality. Turf treated with TE consistently displayed better visual quality than untreated turf regardless of the TE application rate. Repeated applications of TE resulted in less dollar spot disease ( Sclerotinia homeocarpa F.T. Bennett). Applications of TE not only reduced Kentucky bluegrass clipping production but were also effective in managing turfgrass growth. The postsuppression rebound effect can be utilized to manipulate turfgrass growth, allowing the turf to grow rapidly when it is beneficial to do so. No deleterious implications were observed following repeated TE applications.
Modulating the Structure and Properties of Cell Membranes:  The Molecular Mechanism of Action of Dimethyl Sulfoxide (2007)

Dimethyl sulfoxide (DMSO) is a small amphiphilic molecule which is widely employed in cell biology as an effective penetration enhancer, cell fusogen, and cryoprotectant. Despite the vast number of experimental studies, the molecular basis of its action on lipid membranes is still obscure. A recent simulation study employing coarse-grained models has suggested that DMSO induces pores in the membrane (Notman, R.; Noro, M.; O'Malley, B.; Anwar, J. J. Am. Chem. Soc. 2006, 128, 13982-13983). We report here the molecular mechanism for DMSO's interaction with phospholipid membranes ascertained from atomic-scale molecular dynamics simulations. DMSO is observed to exhibit three distinct modes of action, each over a different concentration range. At low concentrations, DMSO induces membrane thinning and increases fluidity of the membrane's hydrophobic core. At higher concentrations, DMSO induces transient water pores into the membrane. At still higher concentrations, individual lipid molecules are desorbed from the membrane followed by disintegration of the bilayer structure. The study provides further evidence that a key aspect of DMSO's mechanism of action is pore formation, which explains the significant enhancement in permeability of membranes to hydrophilic molecules by DMSO as well as DMSO's cryoprotectant activity. The reduction in the rigidity and the general disruption of the membrane induced by DMSO are considered to be prerequisites for membrane fusion processes. The findings also indicate that the choice of DMSO concentration for a given application is critical, as the concentration defines the specific mode of the solvent's action. Knowledge of the distinct modes of action of DMSO and associated concentration dependency should enable optimization of current application protocols on a rational basis and also promote new applications for DMSO.
Cruciform extrusion facilitates intramolecular triplex formation between distal oligopurine.oligopyrimidine tracts: long range effects. (1992)

Two short d(AG)n tracts separated by either of two 40-base pair (bp) inverted repeats adopt a triple-stranded conformation (H-DNA) at the bottom of an extruded cruciform stem in negatively supercoiled plasmids at pH 4.5. Plasmids containing one d(AG)n adjacent to the inverted repeat or containing two d(AG)n tracts separated by a random sequence did not form the triplex structures. These conclusions were derived from chemical modification patterns and UV-sensitivity studies. Two-dimensional agarose gel electrophoresis revealed that the entire insert containing the cruciform and the triplex is locally unlinked. Moreover, a long range structural effect (over 40 bp of random sequence) of one (AG)7 block on the behavior of a second (AG)7 sequence was detected. This effect cannot be transmitted throughout a 50-bp segment of random sequence. A GenBank search revealed the frequent occurrence of short oligopurine blocks with an intervening random sequence of 17-40 bp.
A Cytokine-Centric View of the Pathogenesis and Treatment of Autoimmune Arthritis (2011)

Cytokines are immune mediators that play an important role in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease that targets the synovial joints. The cytokine environment in the peripheral lymphoid tissues and the target organ (the joint) has a strong influence on the outcome of the initial events that trigger autoimmune inflammation. In susceptible individuals, these events drive inflammation and tissue damage in the joints. However, in resistant individuals, the inflammatory events are controlled effectively with minimal or no overt signs of arthritis. Animal models of human RA have permitted comprehensive investigations into the role of cytokines in the initiation, progression, and recovery phases of autoimmune arthritis. The discovery of interleukin-17 (IL-17) and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of arthritis, which previously was based on a simplistic T helper 1 (Th1)-Th2 paradigm. This review discusses the role of the newer cytokines, particularly those associated with the IL-17/IL-23 axis in arthritis. Also presented herein is the emerging information on IL-32, IL-33, and IL-35. Ongoing studies examining the role of the newer cytokines in the disease process would improve understanding of RA as well as the development of novel cytokine inhibitors that might be more efficacious than the currently available options.
Compact spatial multiplexers for mode division multiplexing (2014)

Spatial multiplexer (SMUX) for mode division multiplexing (MDM) has evolved from mode-selective excitation, multiple-spot and photonic-lantern based solutions in order to minimize both mode-dependent loss (MDL) and coupler insertion loss (CIL). This paper discusses the implementation of all the three solutions by compact components in a small footprint. Moreover, the compact SMUX can be manufactured in mass production and packaged to assure high reliability. First, push-pull scheme and center launch based SMUXes are demonstrated on two mostly-popular photonic integration platforms: Silicon-on-insulator (SOI) and Indium Phosphide (InP) for selectively exciting LP<sub>01</sub> and LP<sub>11</sub> modes. 2-dimensional (2D) top-coupling by using vertical emitters is explored to provide a coupling interface between a few-mode fiber (FMF) and the photonic integrated SMUX. SOI-based grating couplers and InP-based 45° vertical mirrors are proposed and researched as vertical emitters in each platform. Second, a 3-spot SMUX is realized on an InP-based circuit through employing 45° vertical mirrors. Third, as a newly-emerging photonic integration platform, laser-inscribed 3D waveguide (3DW) technology is applied for a fully-packaged dual-channel 6-mode SMUX including two 6-core photonic lantern structures as mode multiplexer and demultiplexer, respectively.
Intracellular protein topogenesis (1980)

Concurrently with or shortly after their synthesis on ribosomes, numerous specific proteins are unidirectionally translocated across or asymmetrically integrated into distinct cellular membranes. Thereafter, subpopulations of these proteins need to be sorted from each other and routed for export or targeted to other intracellular membranes or compartments. It is hypothesized here that the information for these processes, termed "protein topogenesis," is encoded in discrete "topogenic" sequences that constitute a permanent or transient part of the polypeptide chain. The repertoire of distinct topogenic sequences is predicted to be relatively small because many different proteins would be topologically equivalent-i.e., targeted to the same intracellular address. The information content of topogenic sequences would be decoded and processed by distinct effectors. Four types of topogenic sequences could be distinguished: signal sequences, stop-transfer sequences, sorting sequences, and insertion sequences. Signal sequences initiate translocation of proteins across specific membranes. They would be decoded and processed by protein translocators that, by virtue of their signal sequence-specific domain and their unique location in distinct cellular membranes, effect unidirectional translocation of proteins across specific cellular membranes. Stop-transfer sequences interrupt the translocation process that was previously initiated by a signal sequence and, by excluding a distinct segment of the polypeptide chain from translocation, yield asymmetric integration of proteins into translocation-competent membranes. Sorting sequences would act as determinants for posttranslocational traffic of subpopulations of proteins, originating in translocation-competent donor membranes (and compartments) and going to translocation-incompetent receiver membranes (and compartments). Finally, insertion sequences initiate unilateral integration of proteins into the lipid bilayer without the mediation of a distinct protein effector. Examples are given for topogenic sequences, either alone or in combination, to provide the information for the location of proteins in any of the intracellular compartments or for the asymmetric orientation of proteins and their location in any of the cellular membranes. Proposals are made concerning the evolution of topogenic sequences and the relationship of protein topogenesis to the precellular evolution of membranes and compartments.
Novel Flexible-Format Optical Modulator with Selectable Combinations of Carrier Numbers and Modulation Levels Based on Silica-PLC and LiNbO3 Hybrid Integration (2011)

We devised a novel flexible-format optical modulator that can optically select optimum sets of carrier numbers and modulation levels according to transmission conditions. The modulator with PLC-LN hybrid integration was successfully operated at 200 Gbps.