gebhart/patrepeval huggingface dataset:
Effective Coulomb interaction in transition metals from constrained random-phase approximation (2011)

The effective on-site Coulomb interaction (Hubbard $U$) between localized $d$ electrons in 3$d$, 4$d$, and 5$d$ transition metals is calculated employing a parameter-free realization of the constrained random-phase approximation using Wannier functions within the full-potential linearized augmented-plane-wave method. The $U$ values lie between 1.5 and 5.7 eV and depend on the crystal structure, spin polarization, $d$ electron number, and $d$ orbital filling. On the basis of the calculated $U$ parameters, we discuss the strength of the electronic correlations and the instability of the paramagnetic state toward the ferromagnetic one for 3$d$ metals.
The relations between ionic and non-ionic diffusion of sulfonamides across the rabbit cornea. (1986)

We studied the transcorneal permeability of five carbonic anhydrase inhibitors, with particular attention to the passage of these acidic compounds in their ionized and nonionized forms. Their pKs varied from 5.9 to 8.0, and CHCl3/pH 7.2 buffer partition coefficients from 10(-4) to 25. Solutions of appropriate pH of each compound were applied to the cornea in steady state, and the rates of passage to the anterior chamber for each compound in each form were measured. The rate constants for the ionized forms were surprisingly high, only four- to sevenfold less than those for the uncharged species. Thus these compounds penetrate the cornea in both forms, and the data show that by increasing the pH of solutions, and thereby solubility, the overall rates of accumulation in the eye are increased.
Reactive Oxygen Species Inhibit Adhesion of Mesenchymal Stem Cells Implanted into Ischemic Myocardium via Interference of Focal Adhesion Complex (2010)

The integrity of transplanted mesenchymal stem cells (MSCs) for cardiac regeneration is dependent on cell-cell or cell-matrix adhesion, which is inhibited by reactive oxygen species (ROS) generated in ischemic surroundings after myocardial infarction. Intracellular ROS play a key role in the regulation of cell adhesion, migration, and proliferation. This study was designed to investigate the role of ROS on MSC adhesion. In H(2)O(2) treated MSCs, adhesion and spreading were inhibited and detachment was increased in a dose-dependent manner, and these effects were significantly rescued by co-treatment with the free radical scavenger, N-acetyl-L-cysteine (NAC, 1 mM). A similar pattern was observed on plates coated with different matrices such as fibronectin and cardiogel. Hydrogen peroxide treatment resulted in a marked decrease in the level of focal adhesion-related molecules, such as phospho-FAK and p-Src in MSCs. We also observed a significant decrease in the integrin-related adhesion molecules, alpha V and beta1, in H(2)O(2) treated MSCs. When injected into infarcted hearts, the adhesion of MSCs co-injected with NAC to the border region was significantly improved. Consequently, we observed that fibrosis and infarct size were reduced in MSC and NAC-injected rat hearts compared to in MSC-only injected hearts. These results indicate that ROS inhibit cellular adhesion of engrafted MSCs and provide evidence that the elimination of ROS might be a novel strategy for improving the survival of engrafted MSCs.
Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells (1994)

Herpes simplex virus (HSV) glycoproteins E and I (gE and gI) can act as a receptor for the Fc domain of immunoglobulin G (IgG). To examine the role of HSV IgG Fc receptor in viral pathogenesis, rabbits and mice were infected by the corneal route with HSV gE- or gI- mutants. Wild-type HSV-1 produced large dendritic lesions in the corneal epithelium and subsequent stromal disease leading to viral encephalitis, whereas gE- and gI- mutant viruses produced microscopic punctate or small dendritic lesions in the epithelium and no corneal disease or encephalitis. These differences were not related to the ability of the gE-gI oligomer to bind IgG because the differences were observed before the appearance of anti-HSV IgG and in mice, in which IgG binds to the Fc receptor poorly or not at all. Mutant viruses produced small plaques on monolayers of normal human fibroblasts and epithelial cells. Replication of gE- and gI- mutant viruses in human fibroblasts were normal, and the rates of entry of mutant and wild-type viruses into fibroblasts were similar; however, spread of gE- and gI- mutant viruses from cell to cell was significantly slower than that of wild-type HSV-1. In experiments in which fibroblast monolayers were infected with low multiplicities of virus and multiple rounds of infection occurred, the presence of neutralizing antibodies in the culture medium caused the yields of mutant viruses to drop dramatically, whereas there was a lesser effect on the production of wild-type HSV. It appears that cell-to-cell transmission of wild-type HSV-1 occurs by at least two mechanisms: (i) release of virus from cells and entry of extracellular virus into a neighboring cell and (ii) transfer of virus across cell junctions in a manner resistant to neutralizing antibodies. Our results suggest that gE- and gI- mutants are defective in the latter mechanism of spread, suggesting the possibility that the gE-gI complex facilitates virus transfer across cell junctions, a mode of spread which may predominate in some tissues. It is ironic that the gE-gI complex, usually considered an IgG Fc receptor, may, through its ability to mediate cell-to-cell spread, actually protect HSV from IgG in a manner different than previously thought.
Immunological Applications of Stem Cells in Type 1 Diabetes (2011)

Current approaches aiming to cure type 1 diabetes (T1D) have made a negligible number of patients insulin-independent. In this review, we revisit the role of stem cell (SC)-based applications in curing T1D. The optimal therapeutic approach for T1D should ideally preserve the remaining β-cells, restore β-cell function, and protect the replaced insulin-producing cells from autoimmunity. SCs possess immunological and regenerative properties that could be harnessed to improve the treatment of T1D; indeed, SCs may reestablish peripheral tolerance toward β-cells through reshaping of the immune response and inhibition of autoreactive T-cell function. Furthermore, SC-derived insulin-producing cells are capable of engrafting and reversing hyperglycemia in mice. Bone marrow mesenchymal SCs display a hypoimmunogenic phenotype as well as a broad range of immunomodulatory capabilities, they have been shown to cure newly diabetic nonobese diabetic (NOD) mice, and they are currently undergoing evaluation in two clinical trials. Cord blood SCs have been shown to facilitate the generation of regulatory T cells, thereby reverting hyperglycemia in NOD mice. T1D patients treated with cord blood SCs also did not show any adverse reaction in the absence of major effects on glycometabolic control. Although hematopoietic SCs rarely revert hyperglycemia in NOD mice, they exhibit profound immunomodulatory properties in humans; newly hyperglycemic T1D patients have been successfully reverted to normoglycemia with autologous nonmyeloablative hematopoietic SC transplantation. Finally, embryonic SCs also offer exciting prospects because they are able to generate glucose-responsive insulin-producing cells. Easy enthusiasm should be mitigated mainly because of the potential oncogenicity of SCs.
Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects (2010)

Asenapine is a psychopharmacologic agent approved in the United States for the acute treatment of schizophrenia in adults and the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. It is pending approval for the treatment of schizophrenia and manic episodes associated with bipolar I disorder in Europe. Asenapine is administered as a sublingual formulation. To determine whether the pharmacokinetics of asenapine are impacted by placing the tablet buccally ('cheeking') or allowing the tablet to dissolve on the top of the tongue, pharmacokinetics were compared following buccal and supralingual administration versus sublingual administration. In this open-label, randomized, 3-way crossover trial, healthy men (n=36) received single 5 mg doses of asenapine via sublingual, supralingual and buccal routes, at least 1 week apart. With buccal administration, the area under the concentration-over-time curve (AUC(0-infinity)) and peak concentration (C(max)) were, respectively, 24%, and 19% higher than with sublingual administration; these routes were not bioequivalent. With supralingual administration, AUC(0-infinity) and C(max) were 6% and 13% lower than with sublingual administration; bioequivalence was established based on AUC(0-infinity) only; bioequivalence based on C(max) could not be assessed due to 40% within-subject variability. The most common adverse events were oral paresthesia (sublingual, 75.8%; supralingual, 55.9%; buccal, 45.7%) and somnolence (81.8%; 76.5%; 68.6%). Compared with the recommended sublingual route of asenapine administration, exposure was 24% higher with buccal administration and comparable to supralingual administration. However, differences in exposure associated with variable placement in the oral cavity did not compromise safety in healthy subjects.
Effect of Pentoxifylline on Carbohydrate Metabolism in Type II Diabetics (1990)

<i>To the Editor</i>. — During the past years we have seen two patients with advanced type II diabetes mellitus (non— insulin-dependent diabetes mellitus), macroangiopathy and microangiopathy, and intermittent claudication. They responded poorly to treatment with sulfonylureas and were given insulin. Their metabolic balance remained inadequate. Because of intermittent claudication, they were given 400 mg of pentoxifylline (Trental) orally three times a day. Without changing the insulin dose, adequate balance was obtained in carbohydrate metabolism as seen in blood and urine glucose levels and glycosylated hemoglobin A<sub>1c</sub>levels. After 2 months of treatment, there was also improvement in walking distance. One of the patients continued to receive the "second-generation" sulfonylurea preparation, glyburide (DiaBeta), throughout this course of treatment. It is assumed that the mechanism of action of sulfonylureas is based on (1) increased insulin secretion by the beta cells of the pancreas, (2) suppression of glucagon and hepatic glucose production,
Polymers and Macromolecules (1988)

Polymers are used widely in pharmaceutical systems as adjuvants, suspending and emulsifying agents, flocculating agents, adhesives, packaging and coating materials, and increasingly as the basis of drug delivery systems.
MASSIT - Multiresolution Analysis of Signal Subspace Invariance Technique: a novel algorithm for blind source separation (2001)

We developed (2001) a novel approach for blind source separation in multichannel signal processing environments. The technique, which relies on an inherent invariance property of the signal subspace across multiresolution levels obtained in the wavelet transform domain, showed robustness to amplitude and shift variations encountered in multi-unit neural recording environments. In this work, we extend the previous work to describe in detail a fast implementation of the algorithm and outline the criterion based on which the characterization of each source should be formulated. Results and performance evaluation that were not reported in the previous paper are illustrated in this paper.
Treatment of Low-Grade Bulbar Transitional Cell Carcinoma with Urethral Instillation of Mitomycin C (2008)

A 63-year old man was referred to us after three rapid recurrences of low-grade urethral papillary transitional cell carcinoma of the bulbar urethra, after repeated primary excision. Cystoscopy confirmed 3-4 low-grade urethral transitional cell carcinomas, which were subsequently fulgurated. After urethral healing, a solution of Mitomycin C (40 mg/80 cc) was instilled into the urethra for fifteen minutes and held in place with a penile clamp. Urethral instillations were repeated weekly for six weeks. The patient is currently disease-free more than one year and three months posttreatment. This case highlights the successful treatment of urethral carcinoma with topical chemotherapy, which is usually reserved for the bladder, using a slight modification of standard technique.
Improved Survival of Follicular Lymphoma Patients in the United States (2005)

The survival of patients with FL in the United States has improved over the last 25 years. The survival improvement may be a result of the sequential application of effective therapies and improved supportive care.
Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription (2005)

The serotonin transporter (5HTT; chromosomal location 17q12) is an important regulator of serotonergic neurotransmission and is the site of action for a number of antidepressant medications. Sequence variation at a VNTR known as the 5HTTLPR, which is 1.4 kb upstream of the translation start of 5HTT, has been associated in some studies with increased vulnerability to depression, neuroticism, and autism. Support for these clinical observations has included laboratory findings that 5HTTLPR variation is associated with changes in 5HTT gene translation. We re-examined these earlier laboratory findings by directly measuring 5HTT mRNA levels and genotyping four loci spanning the 5HTT gene using RNA and DNA prepared from 85 independent lymphoblast cell lines. Using this data, haplotypes were inferred and the resulting single point and haplotypes data analyzed by univariate and regression analyses. Consistent with the original findings, we found a significant effect of the 5HTTLPR on mRNA production. In contrast to previous reports, the effect on 5HTT mRNA production appeared to be mediated through an additive, not dominant, mechanism. Neither genotype nor haplotype at three other 5HTT loci were associated with alterations in mRNA production, although the small number of samples homozygous for the three most common haplotypes limits these findings. We conclude that further examination of the role of 5HTT sequence variation in regulating 5HTT mRNA production is warranted.
Novel pH Selective, Highly Lytic Peptides Based on a Chimeric Influenza Hemagglutinin Peptide/Cell Penetrating Peptide Motif (2019)

Delivery of macromolecular cargos such as siRNA to the cytosol after endocytosis remains a critical challenge. Numerous approaches including viruses, lipid nanoparticles, polymeric constructs, and various peptide-based approaches have yet to yield a general solution to this delivery issue. In this manuscript, we describe our efforts to design novel endosomolytic peptides that could be used to facilitate the release of cargos from a late endosomal compartment. These amphiphilic peptides, based on a chimeric influenza hemagglutinin peptide/cell-penetrating peptide (CPP) template, utilize a pH-triggering mechanism in which the peptides are protonated after acidification of the endosome, and thereby adopt an alpha-helical conformation. The helical forms of the peptides are lytically active, while the non-protonated forms are much less or non-lytically active at physiological pH. Starting from an initial lead peptide (INF7-Tat), we systematically modified the sequence of the chimeric peptides to obtain peptides with greatly enhanced lytic activity that maintain good pH selectivity in a red blood cell hemolysis assay.
Cyclophosphamide (Cy)-facilitated adoptive immunotherapy of a Cy-resistant tumour. Evidence that Cy permits the expression of adoptive T-cell mediated immunity by removing suppressor T cells rather than by reducing tumour burden. (1988)

A cyclophosphamide (Cy)-resistant immunogenic tumour, the L5178Y lymphoma, was used to demonstrate that Cy-treatment of a host bearing this tumour enables passively transferred tumour-sensitized T cells to cause complete tumour regression without any need for Cy to cause a reduction in tumour burden. It was shown that whereas infusion of tumour-sensitized T cells from immune donors had very little effect on growth of the tumour, and whereas treatment with 150 mg/kg of Cy caused appreciable enhancement of tumour growth, combination therapy with Cy plus immune T cells caused complete tumour regression and resulted in long-term survival. Evidence that Cy treatment facilitated the expression of adoptive immunity against the L5178Y lymphoma by eliminating tumour-induced suppressor T cells consisted of the demonstration that tumour regression caused by combination treatment with Cy and immune T cells could be inhibited by infusing the recipient with Cy-sensitive, L3T4+ T cells from tumour-bearing but not from normal donors.
High-yield DNA-templated assembly of surfactant-wrapped carbon nanotubes (2005)

We have developed a straightforward approach for constructing single-walled carbon nanotube (SWNT) assemblies by using aligned surface DNA as a positioning template. A cationic surfactant, dodecyltrimethylammonium bromide, is utilized to suspend SWNTs in aqueous media and localize them on DNA through electrostatic interactions. SWNT positioning is controlled by the surface DNA arrangement, and the extent of deposition is influenced by the SWNT concentration. With lower-concentration SWNT suspensions, multiple surface treatments can increase the DNA coverage. Under optimized conditions, 83% of the length of surface DNAs was covered with SWNTs, and 76% of all surface-deposited SWNTs were on the DNA. In some regions, nearly continuous SWNT assemblies were formed. This approach should provide a useful tool for the fabrication of nanotube nanowires in nanoelectronic circuits.
Evidence for a Novel Gene Associated With Low Tumor Metastatic Potential (1988)

We describe a gene, NM23, that is associated with the tumor metastatic process. NM23 RNA levels were highest in cells and tumors of relatively low metastatic potential in two experimental systems: (1) murine K-1735 melanoma cell lines, in which the gene was identified, and (2) N-nitroso-N-methylurea-induced rat mammary carcinomas. NM23 RNA levels did not correlate with cell sensitivity to host immunological responses and may, therefore, be associated with intrinsic aggressiveness. The predicted carboxy-terminal protein sequence encoded by the pNM23 cDNA clone is novel compared with Genebank animal, bacterial, and viral sequences.
hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. (1999)

The human homologue of the yeast OGG1 gene, hOGG1, has been cloned, and its genetic structure has been determined. Several polymorphisms in the hOGG1 gene were detected in the Japanese populations, and among them, the Ser-Cys polymorphism at codon 326 has been shown to have a functional difference in complementation of mutant Escherichia coli that is defective in the repair of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greater in hOGG1-Ser326 protein than in hOGG1(326) protein. Because many environmental carcinogens produce 8-hydroxyguanine residue and mismatching to this modified base potentially causes oncogenic mutations, the capacity to repair these lesions can be involved in cancer susceptibility in human beings. We, therefore, examined allele distributions of the Ser326Cys polymorphism in a case-control study of male lung cancer in Okinawa. The analyses based on 241 cases and 197 hospital controls disclosed the following findings. (a) Those with the Cys/Cys genotype were at an increased risk of squamous cell carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and those with the Ser/Ser genotypes combined. The odds ratios adjusted for age and smoking history were 3.01 (95% confidence interval, 1.33-6.83) and 2.18 (95% confidence interval, 1.05-4.54), respectively. (b) The odds ratios for other histological subtypes of lung cancer or those in total were not significant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not reach statistical significance in any cell type. (c) The distributions of this polymorphism varied for different populations (Chinese, Japanese, Micronesians, Melanesians, Hungarians, and Australian Caucasians), with much less prevalence of Cys allele in the latter three populations. Although our sample size was limited, these results indicate that the Ser326Cys variant may be related to squamous cell lung cancer susceptibility. The Cys/Cys genotype appears to be more susceptible to squamous cell carcinoma, although the risk is less than that previously reported to be associated with the CYP1A1 gene. Further studies are needed to assess the importance of the interpopulation variation to cancer susceptibility.
Microstimulation in visual area MT: effects on direction discrimination performance (1992)

Physiological and behavioral evidence suggests that the activity of direction selective neurons in visual cortex underlies the perception of moving visual stimuli. We tested this hypothesis by measuring the effects of cortical microstimulation on perceptual judgements of motion direction. To accomplish this, rhesus monkeys were trained to discriminate the direction of motion in a near-threshold, stochastic motion display. For each experiment, we positioned a microelectrode in the middle of a cluster of neurons that shared a common preferred direction of motion. The psychophysical task was then adjusted so that the visual display was presented directly over the neurons' receptive field. The monkeys were required to discriminate between motion shown either in the direction preferred by the neurons or in the opposite direction. On half the trials of an experiment, we applied electrical microstimulation while monkeys viewed the motion display. We hypothesized that enhancing the neurons' discharge rate would introduce a directionally specific signal into the cortex and thereby influence the monkeys' choices on the discrimination task. We compared the monkeys' performance on "stimulated" and "nonstimulated" trials in 139 experiments; all trials within an experiment were presented in random order. Statistically significant effects of microstimulation were obtained in 89 experiments. In 86 of the 89 experiments with significant effects (97%), the monkeys indicated that motion was in the neurons' preferred direction more frequently on stimulated trials than on nonstimulated trials. The data demonstrate a functional link between the activity of direction selective neurons and perceptual judgements of motion direction.
Danazol treatment of advanced breast cancer. (1981)

Danazol, an effective agent in the treatment of benign breast disease, has been administrated to 41 patients with advanced breast cancer. These patients were treated with danazol for periods ranging from 1 to 40 weeks and responses were seen in seven of 41 (17%) patients. No responses were seen in the four premenopausal patients treated. Side effects were seen in nine of 41 (22%) patients, but in most patients these stopped when the dose of danazol was reduced. This preliminary study indicates that danazol may be an effective form of hormone treatment in patients with advanced breast cancer.