gebhart/patrepeval huggingface dataset:
Cognitive and Dissociative Manifestations in Fibromyalgia (2002)

Memory decline and mental confusion frequently complicate the clinical presentation of fibromyalgia; however, formal cognitive examination often does not support deterioration. This paradox was examined in the context of dissociation, a condition with many cognitive similarities. Dissociation refers to the separation of parts of experience from the mainstream of consciousness. A common example is highway hypnosis. Eighty-nine fibromyalgia (FM) patients and 64 other rheumatic disease patients were screened for memory decline and mental confusion using a questionnaire format. Pain, dissociation, affective distress, fatigue, sleep difficulty, and mental confusion were also assessed. Cognitive complaints (76.4%-43.8%) and dissociative symptoms (37.1%-1.9%) were overrepresented in patients with FM. Among FM patients with high dissociation, cognitive difficulties were reported by 95%; 100% of these cases reported that both memory and mental clarity were affected, a condition referred to as fibrofog. Dissociation in combination with fibrofog was associated with higher levels of FM symptom intensity and decreased mental well being. These findings suggest that dissociation may play a role in FM symptom amplification and may aid in comprehending the regularity of cognitive symptoms. Separating cases of fibrofog from cognitive conditions with actual brain damage is important. It may be prudent to add a test of dissociation as an adjunct to the evaluation of FM patients in cases of suspected fibrofog. Otherwise, test results may prove normal even in patients with disabling cognitive symptoms.
Adaptive designs in clinical trials: why use them, and how to run and report them (2018)

Adaptive designs can make clinical trials more flexible by utilising results accumulating in the trial to modify the trial's course in accordance with pre-specified rules. Trials with an adaptive design are often more efficient, informative and ethical than trials with a traditional fixed design since they often make better use of resources such as time and money, and might require fewer participants. Adaptive designs can be applied across all phases of clinical research, from early-phase dose escalation to confirmatory trials. The pace of the uptake of adaptive designs in clinical research, however, has remained well behind that of the statistical literature introducing new methods and highlighting their potential advantages. We speculate that one factor contributing to this is that the full range of adaptations available to trial designs, as well as their goals, advantages and limitations, remains unfamiliar to many parts of the clinical community. Additionally, the term adaptive design has been misleadingly used as an all-encompassing label to refer to certain methods that could be deemed controversial or that have been inadequately implemented.We believe that even if the planning and analysis of a trial is undertaken by an expert statistician, it is essential that the investigators understand the implications of using an adaptive design, for example, what the practical challenges are, what can (and cannot) be inferred from the results of such a trial, and how to report and communicate the results. This tutorial paper provides guidance on key aspects of adaptive designs that are relevant to clinical triallists. We explain the basic rationale behind adaptive designs, clarify ambiguous terminology and summarise the utility and pitfalls of adaptive designs. We discuss practical aspects around funding, ethical approval, treatment supply and communication with stakeholders and trial participants. Our focus, however, is on the interpretation and reporting of results from adaptive design trials, which we consider vital for anyone involved in medical research. We emphasise the general principles of transparency and reproducibility and suggest how best to put them into practice.
Thermolysis of vic-Dihydroxybacteriochlorins:  Effect of the Nature of Substrates in Directing the Formation of Chlorin−Chlorin Dimers with Fixed and Flexible Orientations and Their Preliminary in Vitro Photosensitizing Efficacy (2003)

The thermolysis products obtained by refluxing a series of vic-dihydroxychlorins in o-dichlorobenzene are characterized. Depending on the nature of substrates, this methodology provides an access for novel carbon-carbon linked chlorin-chlorin dimers and chlorin-porphyrin dimers with fixed and flexible orientations. The configuration of the linkers in the symmetrical and unsymmetrical dimers was confirmed by extensive NMR (COSY, ROESY) and molecular modeling studies. The molecular modeling studies of the energy-optimized dimers with flexible orientation confirmed that one of the chlorin units of the dimeric structure is tilted toward the opposite ring as evident by the shielding effect in the resonances of some of the protons in the (1)H NMR spectroscopy. Among the dimers with fixed orientation, compared to the free-base analogues, the related mono- and di-Zn(II) complexes produced a decreased fluorescence intensity, suggesting a possibility of the faster energy transfer via intersystem crossing (ISC) in the metalated derivatives than the corresponding free-base analogues to produce the corresponding excited triplet states. The photosensitizing efficacy of the monomers and the related dimers was also compared in radiation-induced fibrosarcoma (RIF) tumor cells at variable drug/light doses. In preliminary screening, compared to monomers, the corresponding carbon-carbon linked dimers produced enhanced photosensitizing efficacy.
Intracardiac pulsed field ablation: Proof of feasibility in a chronic porcine model (2018)

Intracardiac PFA can be feasibly delivered from a circular catheter to create fibrotic lesions that have acute electrical effects, without injury to nontargeted tissue.
Involvement of Marinobufagenin in a Rat Model of Human Preeclampsia (2005)

These results suggest a relationship between MBG and a syndrome in rats resembling preeclampsia. Armed with these promising results, it would seem logical to further examine the role of MBG in human preeclampsia.
Intracellular translocation of fluorescent sphingolipids in cultured fibroblasts: endogenously synthesized sphingomyelin and glucocerebroside analogues pass through the Golgi apparatus en route to the plasma membrane. (1985)

When monolayer cultures of Chinese hamster lung fibroblasts are briefly incubated at 2 degrees C with the fluorescent sphingolipid analogue, C6-NBD-ceramide (N- [7-(4-nitrobenzo-2-oxa-1,3-diazole)] aminocaproyl sphingosine), fluorescent labeling of the mitochondria, endoplasmic reticulum, and nuclear envelope occur. During further incubation at 37 degrees C, the Golgi apparatus, and later the plasma membrane, become intensely fluorescent. Within this period, the C6-NBD-ceramide is converted to equal amounts of fluorescent sphingomyelin and glucocerebroside (Lipsky, N. G., and R. E. Pagano, 1983, Proc. Natl. Acad. Sci. USA., 80:2608-2612). In the present study, the intracellular translocation of these metabolites and their subsequent appearance at the plasma membrane were investigated by fluorescence microscopy, the addition of the ionophore monensin, and the technique of "back exchange," in which the amounts and types of fluorescent lipids present at the cell surface are identified after their transfer from the cell surface into recipient vesicles. In control cells, the amount of fluorescent glucocerebroside and sphingomyelin that could be removed from the cell surface by back exchange increased during incubation at 37 degrees C, correlating with the increased fluorescence of the plasma membrane observed by microscopy. In the presence of 10 microM monensin, visible labeling of the plasma membrane was greatly diminished, whereas the Golgi apparatus became highly fluorescent and distended. The ability to remove fluorescent metabolites from the cell surface by back exchange was significantly but reversibly inhibited by monensin. Monensin also increased the total amount of fluorescent sphingomyelin, but not the glucocerebroside found in cells. Subcellular fractions were assayed for their ability to convert radiolabeled and fluorescent ceramides to the corresponding sphingomyelins and glucocerebrosides. The activities of parallel fractions coincided, suggesting that the presence of the NBD moiety did not affect the cellular metabolism of ceramide. Furthermore, the major peak of sphingomyelin- and glucocerebroside-synthesizing activity appeared to coincide with an enriched Golgi fraction. These results strongly suggest that fluorescent sphingomyelin was not synthesized at the plasma membrane as has recently been suggested for endogenous sphingomyelin. Rather, both the sphingomyelin and glucocerebroside analogues were synthesized intracellularly from C6-NBD-ceramide and translocated through the Golgi apparatus to the cell surface.
Spatial Organization and Composition of the Mucosal Flora in Patients with Inflammatory Bowel Disease (2005)

The composition and spatial organization of the mucosal flora in biopsy specimens from patients with inflammatory bowel disease (IBD; either Crohn's disease or ulcerative colitis), self-limiting colitis, irritable-bowel syndrome (IBS), and healthy controls were investigated by using a broad range of fluorescent bacterial group-specific rRNA-targeted oligonucleotide probes. Each group included 20 subjects. Ten patients who had IBD and who were being treated with antibiotics were also studied. Use of nonaqueous Carnoy fixative to preserve the mucus layer was crucial for detection of bacteria adherent to the mucosal surface (mucosal bacteria). No biofilm was detectable in formalin-fixed biopsy specimens. Mucosal bacteria were found at concentrations greater than 10(9)/ml in 90 to 95% of IBD patients, 95% of patients with self-limiting colitis, 65% of IBS patients, and 35% of healthy controls. The mean density of the mucosal biofilm was 2 powers higher in IBD patients than in patients with IBS or controls, and bacteria were mostly adherent. Bacteroides fragilis was responsible for >60% of the biofilm mass in patients with IBD but for only 30% of the biofilm mass in patients with self-limiting colitis and <15% of the biofilm mass in patients with IBS. In contrast, bacteria which positively hybridized with the probe specific for Eubacterium rectale-Clostridium coccoides accounted for >40% of the biofilm in IBS patients but for <15% of the biofilm in IBD patients. In patients treated with (5-ASA) or antibiotics, the biofilm could be detected with 4,6-diamidino-2-phenylindole but did not hybridize with fluorescence in situ hybridization probes. A Bacteroides fragilis biofilm is the main feature of IBD. This was not previously recognized due to a lack of appropriate tissue fixation. Both 5-ASA and antibiotics suppress but do not eliminate the adherent biofilm.
In VitroLarge Scale Production of Human Mature Red Blood Cells from Hematopoietic Stem Cells by Coculturing with Human Fetal Liver Stromal Cells (2013)

In vitro models of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation in normal and pathological conditions. Here we describe an erythroid liquid culture system starting from cord blood derived hematopoietic stem cells (HSCs). HSCs were cultured for more than 50 days in erythroid differentiation conditions and resulted in a more than 10(9)-fold expansion within 50 days under optimal conditions. Homogeneous erythroid cells were characterized by cell morphology, flow cytometry, and hematopoietic colony assays. Furthermore, terminal erythroid maturation was improved by cosculturing with human fetal liver stromal cells. Cocultured erythroid cells underwent multiple maturation events, including decrease in size, increase in glycophorin A expression, and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to 80% of the cells. Importantly, they possessed the capacity to express the adult definitive β -globin chain upon further maturation. We also show that the oxygen equilibrium curves of the cord blood-differentiated red blood cells (RBCs) are comparable to normal RBCs. The large number and purity of erythroid cells and RBCs produced from cord blood make this method useful for fundamental research in erythroid development, and they also provide a basis for future production of available RBCs for transfusion.
Structure of the platelet membrane glycoprotein IIb. Homology to the alpha subunits of the vitronectin and fibronectin membrane receptors. (1987)

The platelet membrane glycoprotein IIb X IIIa heterodimer complex (GPIIb X IIIa) is the platelet receptor for adhesive proteins, containing binding sites for fibrinogen, von Willebrand factor, and fibronectin on activated platelets. GPIIb X IIIa also appears to be a member of a family of membrane adhesive protein receptors that plays a major role in cell-cell and cell-matrix interactions. GPIb is the larger component of this platelet receptor and is composed of two disulfide-linked subunits. In this report we describe the analysis of cDNA clones for human GPIIb that were isolated from a lambda gt11 expression library prepared using RNA from HEL cells. A total of 3.3 kilobases of cDNA was sequence, revealing a continuous open reading frame encoding both GPIIb subunits. The cDNA encodes 1039 amino acids: 137 constituting the smaller subunit, 871 constituting the larger subunit, and 30 constituting an NH2-terminal signal peptide. No homology was found between the larger and smaller subunits. The smaller subunit contains a 26-residue hydrophobic sequence near its COOH terminus that represents a potential transmembrane domain. Four stretches of 12 amino acids present in the larger subunit are homologous to the calcium binding sites of calmodulin and troponin C. Northern blot analysis using HEL cell RNA indicated that the mature mRNA coding for GPIIb is 4.1 kilobases in size. A comparison of the GPIIb coding region with available cDNA sequences of the alpha-chains of the vitronectin and fibronectin receptors revealed 41% DNA homology and 74% and 63% amino acid homology, respectively. Our data establish the amino acid sequence for the human platelet glycoprotein IIb and provide additional evidence for the existence of a family of cellular adhesion protein receptors.
Mouse Ribonucleotide Reductase Control (2001)

Using ribonucleotide reductase encoded by vaccinia virus as a model for the mammalian enzyme, our laboratory developed an assay that allows simultaneous monitoring of the reduction of ADP, CDP, GDP, and UDP. That study found ADP reduction to be specifically inhibited by ADP itself. To learn whether this effect is significant for cellular regulation, we have analyzed recombinant mouse ribonucleotide reductase. We report that allosteric control properties originally described in single-substrate assays operate also under our four-substrate assay conditions. Three distinctions from the vaccinia enzyme were seen: 1) higher sensitivity to allosteric modifiers; 2) higher activity with UDP as substrate; and 3) significant inhibition by ADP of GDP reduction as well as that of ADP itself. Studies of the effects of ADP and other substrates upon binding of effectors indicate that binding of ribonucleoside diphosphates at the catalytic site influences dNTP binding at the specificity site. We also examined the activities of hybrid ribonucleotide reductases, composed of a mouse subunit combined with a vaccinia subunit. As previously reported, a vaccinia R1/mouse R2 hybrid has low but significant activity. Surprisingly, a mouse R1/vaccinia R2 hybrid was more active than either mouse R1/R2 or vaccinia R1/R2, possibly explaining why mutations affecting vaccinia ribonucleotide reductase have only small effects upon viral DNA replication.
Pregnancy and Interferon-τ Upregulate Gene Expression of Members of the 1-8 Family in the Bovine Uterus1 (2001)

The 1-8 family (1-8U, 1-8D, Leu-13/9-27) of interferon (IFN)-inducible genes encodes proteins that are components of multimeric complexes involved with transduction of antiproliferative and homotypic adhesion signals. Human 1-8 family members are highly similar and are regulated by type 1 and type 2 IFNs. Because the bovine uterus is bathed in conceptus-derived IFN tau during early pregnancy, it was hypothesized that members of the 1-8 family were upregulated in the bovine uterus during early pregnancy. Oligonucleotide primers were designed based on human and rat 1-8U and Leu-13 cDNAs and used in reverse transcription polymerase chain reactions to amplify bovine cDNAs from endometrial RNA. The bovine 1-8U cDNA was sequenced, found to be 84% identical to the human 1-8U, and used to screen a bovine endometrial cDNA library to isolate the full-length 1-8U and Leu-13 cDNAs. The inferred amino acid sequences of bovine 1-8U and Leu-13 were 72% and 73% identical to their respective human counterparts. Bovine 1-8U and Leu-13 retain an amino acid motif that is conserved in other 1-8 family members and in some ubiquitin-conjugating enzymes (E2s). This motif is critical for function of E2s in covalently linking ubiquitin to targeted proteins. Northern blotting revealed that bovine endometrial 1-8U and Leu-13 mRNAs were upregulated on Day 15 of pregnancy (P < 0.0001) and continued to accumulate through Day 18 of pregnancy (P < 0.05) when compared with endometrium from nonpregnant cows. The bovine 1-8U and Leu-13 mRNAs were also upregulated (P < 0.05) by IFN tau (25 nM) within 3 h, continued to accumulate through 12 h, and reached a plateau at 12-24 h in cultured bovine endometrial cells. In situ hybridization revealed that mRNAs encoding 1-8 family members were heavily localized to glandular epithelium but also were present to a lesser extent in the luminal epithelium and stroma. The temporal upregulation of 1-8U and Leu-13 mRNAs by pregnancy and IFN tau and tissue distribution of these mRNAs paralleled closely that of the ubiquitin homolog, IFN-stimulated gene product 17. These IFN-induced proteins probably work together to prepare the endometrium for adhesion of the developing conceptus.
Structural and Electronic Properties of Li-Ion Battery Cathode Material FeF3 (2010)

A new type of cathode materials for Li-ion batteries has been explored recently based on FeF3 in an attempt to raise the energy density and discharge voltage. In this work, the structural and electronic properties of cathode materials FeF3 for lithium ion batteries have been studied by the first-principles calculations within both the generalized gradient approximation (GGA) and GGA+U frameworks. Our results show that the antiferromagnetic configuration of FeF3 is more stable than the ferromagnetic one, which is consistent with experiments. An analysis of the electronic density of states shows that FeF3 is a Mott−Hubbard insulator with a large d−d type band gap. Additionally, a small spin polarization was found on F, consistent with a fluorin-mediated superexchange mechanism for the Fe−Fe magnetic interaction.
Structure and Physical Properties of Tailor-Made Ce,Zr-Doped Carbon Aerogels (2000)

Carbon aerogels with controlled porosity can be obtained by doping the resorcinol–formaldehyde reaction mixture with Ce and/or Zr. As highlighted here, the concentration of metal dopant and the pH of the initial reaction mixture can have a profound effect on the structure, porosity, and physical properties of the resulting aerogel. The Figure shows the morphology of a Ce,Zr-doped carbon aerogel synthesized at pH 7.
Optimization of Active Tendon Controlled Structures by Efficient Solution of LQR Control Gain (2008)

The objective of current study is to develop an optimization technique for the seismic actively controlled building structures using active tendon devices by an efficient solution of LQR control gain. In order to solve the active control system, the Ricatti closed-loop algorithm has been applied, and the state vector has been formulated by the transfer matrix and solved by a numerical technique of the trapezoidal rule. The time-delay problem has been also considered by phase compensation. To optimize the performance index, the ratio of the weighted matrix is the design variable, allowable story drift limits of IBC 2000 and tendon forces have been applied as restraint conditions, and the optimum control program has been developed with the algorithm of the SUMT technique. In examples of the optimization problem of eight stories shear buildings, it is evaluated that the optimum controlled building is more suitable in the control of earthquake response than the uncontrolled system and can reduce the performance index to compare with the controlled system with a constant ratio of the weighted matrix.
Principles of cell-free genetic circuit assembly (2003)

Cell-free genetic circuit elements were constructed in a transcription-translation extract. We engineered transcriptional activation and repression cascades, in which the protein product of each stage is the input required to drive or block the following stage. Although we can find regions of linear response for single stages, cascading to subsequent stages requires working in nonlinear regimes. Substantial time delays and dramatic decreases in output production are incurred with each additional stage because of a bottleneck at the translation machinery. Faster turnover of RNA message can relieve competition between genes and stabilize output against variations in input and parameters.
A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia (1987)

We found a novel platelet aggregating factor in a patient with steroid- responsive immune thrombocytopenic purpura that is associated with defective collagen-induced platelet functions. The aggregating factor and platelet functions were analyzed. The patient, a 58-year-old female, had purpura and prolonged bleeding time despite adequate platelet counts (greater than 140,000/microL) after steroid therapy. The patient's platelets responded normally to all agonists except collagen. Platelet adhesion to collagen fibrils was decreased. The patient's plasma induced irreversible aggregation and ATP release in normal platelet-rich plasma (PRP). This platelet aggregating factor was found in F(ab')2 fragments of the patient's IgG, which caused thromboxane B2 synthesis, elevation of cytoplasmic Ca2+ levels, and phosphorylation of 40 kDa protein in normal platelets. Platelet aggregation by the patient's IgG was inhibited by prostacyclin, dibutyryl cAMP, diltiazem, disodium ethylenediaminetetraacetate, and antimycin A plus iodoacetate, but ADP scavengers, cyclo-oxygenase inhibitors, and heparin had little or no effect. The aggregating activity of the patient's IgG absorbed to and eluted from normal platelets. The patient's Fab fragments did not induce platelet aggregation in eight of ten normal PRP but specifically inhibited aggregation induced by collagen and by the patient's IgG. The major component of an immunoprecipitate made with the patient's IgG from radiolabeled membrane proteins of normal platelet extract had a 62 kDa mol wt, while no such precipitate appeared in extracts of the patient's platelets. These results indicated that platelet aggregation by the patient's IgG was induced by the reaction of an antibody with a specific antigen on the normal platelet membrane through stimulus- response coupling. This antigen may be a collagen receptor on the platelet, most likely a polypeptide of 62 kDa under reducing condition. The defect of collagen-induced aggregation of the patient's platelets seemed to be due to alteration of the membrane protein related to this putative collagen receptor.