gebhart/patrepeval huggingface dataset:
Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells (1993)

Pili have been shown to play an essential role in the adhesion of Neisseria meningitidis to epithelial cells. However, among piliated strains, both inter- and intrastrain variability exist with respect to their degree of adhesion to epithelial cells in vitro (Virji et al., 1992). This suggests that factors other than the presence of pili per se are involved in this process. The N. meningitidis pilin subunit undergoes extensive antigenic variation. Piliated low- and high-adhesive derivatives of the same N. meningitidis strain were selected and the nucleotide sequence of the pilin gene expressed in each was determined. The highly adhesive derivatives had the same pilin sequence. The alleles encoding the pilin subunit of the low-adhesive derivatives were completely different from the one found in the high-adhesive isolates. Using polyclonal antibodies raised against one hyperadhesive variant, it was confirmed that the low-adhesive piliated derivatives expressed pilin variants antigenically different from the highly adhesive strains. The role of antigenic variation in the adhesive process of N. meningitidis was confirmed by performing allelic exchanges of the pilE locus between low- and high-adhesive isolates. Antigenic variation has been considered a means by which virulent bacteria evade the host immune system. This work provides genetic proof that a bacterial pathogen, N. meningitidis, can use antigenic variation to modulate their degree of virulence.
Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice (2010)

TLR ligands are promising candidates for the development of novel vaccine adjuvants that can elicit protective immunity against emerging infectious diseases. Adjuvants have been used most frequently to increase the quantity of an immune response. However, the quality of a T cell response can be more important than its quantity. Stimulating certain pairs of TLRs induces a synergistic response in terms of activating dendritic cells and eliciting/enhancing T cell responses through clonal expansion, which increases the number of responding T cells. Here, we have found that utilizing ligands for 3 TLRs (TLR2/6, TLR3, and TLR9) greatly increased the protective efficacy of vaccination with an HIV envelope peptide in mice when compared with using ligands for only any 2 of these TLRs; surprisingly, increased protection was induced without a marked increase in the number of peptide-specific T cells. Rather, the combination of these 3 TLR ligands augmented the quality of the T cell responses primarily by amplifying their functional avidity for the antigen, which was necessary for clearance of virus. The triple combination increased production of DC IL-15 along with its receptor, IL-15Ralpha, which contributed to high avidity, and decreased expression of programmed death-ligand 1 and induction of Tregs. Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses.
Identification of Porcine Coagulation Factor VIII Domains Responsible for High Level Expression via Enhanced Secretion (2004)

Blood coagulation factor VIII has a domain structure designated A1-A2-B-ap-A3-C1-C2. Human factor VIII is present at low concentration in normal plasma and, comparably, is produced at low levels in vitro and in vivo using transgenic expression techniques. Heterologous expression of B domain-deleted porcine factor VIII in mammalian cell culture is significantly greater than B domain-deleted human or murine factor VIII. Novel hybrid human/porcine factor VIII molecules were constructed to identify porcine factor VIII domains that confer high level expression. Hybrid human/porcine factor VIII constructs containing the porcine factor VIII A1 and ap-A3 domains expressed at levels comparable with recombinant porcine factor VIII. A hybrid construct containing only the porcine A1 domain expressed at intermediate levels between human and porcine factor VIII, whereas a hybrid construct containing the porcine ap-A3 domain expressed at levels comparable with human factor VIII. Additionally, hybrid murine/porcine factor VIII constructs containing the porcine factor VIII A1 and ap-A3 domain sequences expressed at levels significantly higher than recombinant murine factor VIII. Therefore, the porcine A1 and ap-A3 domains are necessary and sufficient for the high level expression associated with porcine factor VIII. Metabolic radiolabeling experiments demonstrated that high level expression was attributable to enhanced secretory efficiency.
Gut hormone changes after jejunoileal (JIB) or biliopancreatic (BPB) bypass surgery for morbid obesity. (1981)

The treatment of obesity by intestinal bypass provides a unique model for the investigation of gut hormone release from the functionally deranged bowel. We have examined the postprandial response of eight circulating gut or pancreatic peptide hormones in 16 preoperative obese patients, 20 patients with jejunoileal bypass, 38 patients with biliopancreatic bypass and 13 age and sex-matched controls. Basal and post-meal hormone concentrations were determined by specific radioimmunoassay methods. Reductions of the upper small intestinal hormones, motilin and gastric inhibitory polypeptide were found in both types of surgery. Conversely, the ileal hormones neurotensin and enteroglucagon were elevated following surgery. This pattern is consistent with the known distribution of these hormones. Variations of response due to surgical differences were noted for gastrin and the enteropancreatic axis, which was more markedly disturbed after biliopancreatic bypass. The alterations of hormone release closely reflect the anatomical changes induced by each particular surgical technique.
Bone graft for tibial defects in total knee arthroplasty. (1986)

Twenty-four knees with bone grafts for tibial defects at the time of either primary or revision total knee arthroplasty were followed for three to six years. With 22 of 24 bone grafts, union and revascularization were seen and no clinical collapse was present. In two, nonunion occurred, accompanied by collapse in one. Failure was attributed to varus alignment of the leg in one (a medial condylar graft) and to insufficient preparation of the bony bed in the second (bleeding bone was not exposed). Evidence for incorporation of the grafts was obtained by tomogram, bone scan, and bone biopsy. Incorporation was present by six months, but the time to complete remodeling was not determined. A bone graft is recommended for tibial defect involving 50% or more of the bony support of either tibial plateau. A bone graft is indicated whenever a cement column under the prosthesis would measure more than 5 mm in height.
Mechanisms of Membrane Transport of Folates into Cells and Across Epithelia (2011)

Until recently, the transport of folates into cells and across epithelia has been interpreted primarily within the context of two transporters with high affinity and specificity for folates, the reduced folate carrier and the folate receptors. However, there were discrepancies between the properties of these transporters and characteristics of folate transport in many tissues, most notably the intestinal absorption of folates, in terms of pH dependency and substrate specificity. With the recent cloning of the proton-coupled folate transporter (PCFT) and the demonstration that this transporter is mutated in hereditary folate malabsorption, an autosomal recessive disorder, the molecular basis for this low-pH transport activity is now understood. This review focuses on the properties of PCFT and briefly addresses the two other folate-specific transporters along with other facilitative and ATP-binding cassette (ABC) transporters with folate transport activities. The role of these transporters in the vectorial transport of folates across epithelia is considered.
Localization of the centrin‐related 165,000‐Mr protein of PtK2 cells during the cell cycle (1991)

In this study, we follow changes in localization of the centrin-related 165,000-Mr protein of PtK2 cells during the cell cycle. This protein is a component of a pericentriolar lattice that consists of pericentriolar satellites, pericentriolar matrix, and basal feet (Baron A.T., and J.L. Salisbury, J. Cell Biol. 107:2669-2678, 1988). By immunofluorescence microscopy, the 165,000-Mr protein is seen as a constellation of pericentrosomal spots. We observe that cells in late G1 and S are characterized by a dense centrosomal focus of spots with additional spots dispersed throughout the cytoplasm. In G2, one bright centrosomal focus of clustered spots is observed. As the cells proceed through prophase this single focus divides, forming two foci that move toward opposite sides of the nucleus. During prometaphase, each polar focus of spots disperses. At metaphase, the spots are distributed throughout each half-cytoplast from the poles to the chromosomes. During anaphase chromosome movement, some spots are seen beside and behind the trailing chromosome arms while others are clustered at the poles. At telophase, pericentrosomal spots radiate from the poles to surround each mass of chromatin. In early G1, pericentrosomal spots surround each newly formed nucleus. We conclude that the 165,000-Mr protein is a dynamic component of both the centrosome (pericentriolar matrix) and the mitotic apparatus (spindle matrix).
Long term pharmacotherapy for obesity and overweight: updated meta-analysis (2007)

Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.
Somatostatin inhibits the activity of adenylate cyclase in cultured human meningioma cells and stimulates their growth. (1992)

It has been reported previously that most human meningiomas have receptors for somatostatin. Here we report the results of investigations of the effect of somatostatin and the somatostatin analog octreotide on the growth in vitro of human meningioma cells. Neither somatostatin nor its analog showed a direct growth inhibitory action on cultured human meningioma cells. Rather, there was a slight but significant stimulation of growth in the presence of somatostatin. The somatostatin receptors in meningioma tissue were shown to be functional since somatostatin inhibited forskolin-stimulated formation of cAMP by meningioma membranes. In addition, cAMP inhibited the growth of cultured meningioma cells. We conclude that the stimulation by somatostatin of the growth of human meningioma cells in vitro is caused by its inhibitory effect on cAMP formation. These results suggest that therapeutic trials of patients with (recurrent) inoperable meningiomas with somatostatin analogs have to be carried out with great caution.
Hidden layers of human small RNAs (2008)

Our results underscore the complexity of the small RNA world and the biogenesis of small RNAs.
Biomaterials‐based organic electronic devices (2010)

Organic electronic devices have demonstrated tremendous versatility in a wide range of applications including consumer electronics, photovoltaics, and biotechnology. The traditional interface of organic electronics with biology, biotechnology, and medicine occurs in the general field of sensing biological phenomena. For example, the fabrication of hybrid electronic structures using both organic semiconductors and bioactive molecules has led to enhancements in sensitivity and specificity within biosensing platforms, which in turn has a potentially wide range of clinical applications. However, the interface of biomolecules and organic semiconductors has also recently explored the potential use of natural and synthetic biomaterials as structural components of electronic devices. The fabrication of electronically active systems using biomaterials-based components has the potential to realize a large set of unique devices including environmentally biodegradable systems and bioresorbable temporary medical devices. This article reviews recent advances in the implementation of biomaterials as structural components in organic electronic devices with a focus on potential applications in biotechnology and medicine.
Highly Stretchable, Global, and Distributed Local Strain Sensing Line Using GaInSn Electrodes for Wearable Electronics (2015)

For identifying human or finger movement, it is necessary to sense subtle movements at multiple points, including the local strain and global deformation simultaneously; however, this has not yet been realized. Therefore, a highly stretchable, global, and distributed local strain sensing electrode made of GaInSn and polydimethylsiloxane is developed for wearable devices. To investigate the electrical properties of multiple sections of the GaInSn electrode when stretching, tensile, cyclic, and three‐point‐bending tests are performed. The results demonstrate that the electrode can withstand a strain up to 50% and has little hysteresis without any delay. Moreover, the distributed local strain and global strain can be simultaneously measured using just a single electrode line. Finally, a prototype of a data glove as an application of the strain sensing line is manufactured, and it is demonstrated that the folding state of fingers could be identified. The proposed technology may allow the creation of a lightweight master hand manipulator or 3D data entry device.
Multi-camera simultaneous localization and mapping (2019)

In this thesis, we study two aspects of simultaneous localization and mapping (SLAM) for multi-camera systems: minimal solution methods for the scaled motion of non-overlapping and partially overlapping two camera systems and enabling online, real-time mapping of large areas using the parallelism inherent in the visual simultaneous localization and mapping (VSLAM) problem. We present the only existing minimal solution method for six degree of freedom structure and motion estimation using a non-overlapping, rigid two camera system with known intrinsic and extrinsic calibration. One example application of our method is the three-dimensional reconstruction of urban scenes from video. Because our method does not require the cameras' fields-of-view to overlap, we are able to maximize coverage of the scene and avoid processing redundant, overlapping imagery. Additionally, we developed a minimal solution method for partially overlapping stereo camera systems to overcome degeneracies inherent to non-overlapping two-camera systems but still have a wide total field of view. The method takes two stereo images as its input. It uses one feature visible in all four views and three features visible across two temporal view pairs to constrain the system camera's motion. We show in synthetic experiments that our method creates rotation and translation estimates that are more accurate than the perspective three-point method as the overlap in the stereo camera's fields-of-view is reduced. A final part of this thesis is the development of an online, real-time visual SLAM system that achieves real-time speed by exploiting the parallelism inherent in the VSLAM problem. We show that feature tracking, relative pose estimation, and global mapping operations such as loop detection and loop correction can be effectively parallelized. Additionally, we demonstrate that a combination of short baseline, differentially tracked corner features, which can be tracked at high frame rates and wide baseline matchable but slower to compute features such as the scale-invariant feature transform can facilitate high speed visual odometry and at the same time support location recognition for loop detection and global geometric error correction.
Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. (1982)

Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.
n-Tetradecanoyl is the NH2-terminal blocking group of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle. (1982)

The unusual NH2-terminal blocking group of the catalytic subunit of bovine cardiac muscle cyclic AMP-dependent protein was found to be amide-linked n-tetradecanoic acid by gas chromatographic-, direct chemical ionization-, and fast atom bombardment-mass spectrometry. In addition, fast atom bombardment mass spectrometry revealed the presence of an additional alanine which had been overlooked when the original sequence was determined. The corrected and completed NH2-terminal sequence of the 350-amino acid catalytic subunit is CH3(CH2)12CONH-Gly-Asn-Ala-Ala-Ala-Ala-Lys.
PNA microarrays for hybridisation of unlabelled DNA samples (2003)

Several strategies have been developed for the production of peptide nucleic acid (PNA) microarrays by parallel probe synthesis and selective coupling of full-length molecules. Such microarrays were used for direct detection of the hybridisation of unlabelled DNA by time-of-flight secondary ion mass spectrometry. PNAs were synthesised by an automated process on filter-bottom microtitre plates. The resulting molecules were released from the solid support and attached without any purification to microarray surfaces via the terminal amino group itself or via modifications, which had been chemically introduced during synthesis. Thus, only full-length PNA oligomers were attached whereas truncated molecules, produced during synthesis because of incomplete condensation reactions, did not bind. Different surface chemistries and fitting modifications of the PNA terminus were tested. For an examination of coupling selectivity, bound PNAs were cleaved off microarray surfaces and analysed by MALDI-TOF mass spectrometry. Additionally, hybridisation experiments were performed to compare the attachment chemistries, with fully acetylated PNAs spotted as controls. Upon hybridisation of unlabelled DNA to such microarrays, binding events could be detected by visualisation of phosphates, which are an integral part of nucleic acids but missing entirely in PNA probes. Overall best results in terms of selectivity and sensitivity were obtained with thiol-modified PNAs on maleimide surfaces.
The significance of morphological changes in cerebral arteries after subarachnoid hemorrhage (1990)

A porcine model was developed to allow quantitative assessment of morphological changes in cerebral arteries after subarachnoid hemorrhage and to determine the significance of structural changes in producing arterial narrowing. Whole blood was selectively applied to the middle cerebral artery (MCA) of seven pigs. After 10 days, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. The MCA's exposed to whole blood for 10 days showed prominent luminal narrowing associated with profound ultrastructural changes affecting all layers of the vessel wall. Morphometric analysis, however, demonstrated that significant reductions in the luminal cross-sectional area (-55.8% +/- 12.5%, p less than 0.005) and increases in radial wall thickness (75.1% +/- 10.5%, p less than 0.005) were associated with only minimal increase in the cross-sectional area of the vessel wall (12.5% +/- 15%, p less than 0.025). By stereological analysis, the volume density of individual components of the arterial wall was unchanged in MCA's exposed to blood. Vessels exposed to blood showed a 44% reduction in smooth-muscle cell immunoreactive actin and increased collagen in the extracellular matrix of the vessel wall. These data suggest that structural changes in cerebral arteries after subarachnoid hemorrhage do not directly contribute to vessel narrowing through increases in wall mass. Nevertheless, such changes may reflect pathological mechanisms which act to augment prolonged vasoconstriction or inhibit the maintenance of normal vascular tone.
762. Griseofulvin. Part IV. Structure (1952)

J. F. Grove, J. MacMillan, T. P. C. Mulholland and M. A. T. Rogers, J. Chem. Soc., 1952, 3977 DOI: 10.1039/JR9520003977
Systematic exploration of a class of hydrophobic unnatural base pairs yields multiple new candidates for the expansion of the genetic alphabet (2014)

We have developed a family of unnatural base pairs (UBPs), which rely on hydrophobic and packing interactions for pairing and which are well replicated and transcribed. While the pair formed between d5SICS and dNaM (d5SICS-dNaM) has received the most attention, and has been used to expand the genetic alphabet of a living organism, recent efforts have identified dTPT3-dNaM, which is replicated with even higher fidelity. These efforts also resulted in more UBPs than could be independently analyzed, and thus we now report a PCR-based screen to identify the most promising. While we found that dTPT3-dNaM is generally the most promising UBP, we identified several others that are replicated nearly as well and significantly better than d5SICS-dNaM, and are thus viable candidates for the expansion of the genetic alphabet of a living organism. Moreover, the results suggest that continued optimization should be possible, and that the putatively essential hydrogen-bond acceptor at the position ortho to the glycosidic linkage may not be required. These results clearly demonstrate the generality of hydrophobic forces for the control of base pairing within DNA, provide a wealth of new structure-activity relationship data and importantly identify multiple new candidates for in vivo evaluation and further optimization.