gebhart/patrepeval huggingface dataset:
A critical analysis of linear inverse solutions to the neuroelectromagnetic inverse problem (1998)

This paper explores the possibilities of using linear inverse solutions to reconstruct arbitrary current distributions within the human brain. We formally prove that due to the underdetermined character of the problem, the only class of measurable current distributions that can be totally retrieved are those of minimal norm. The reconstruction of smooth or averaged versions of the currents is also explored. A solution that explicitly attempts to reconstruct averages of the current is proposed and compared with the minimum norm and the minimum Laplacian solution. In contrast to the majority of previous analysis carried out in the field, in the comparisons, we avoid the use of measures designed for the case of dipolar sources. To allow for the evaluation of distributed solutions in the case of arbitrary current distributions we use the concept of resolution kernels. Two summarizing measures, source identifiability and source visibility, are proposed and applied to the comparison. From this study can be concluded: 1) linear inverse solutions are unable to produce adequate estimates of arbitrary current distributions at many brain sites and 2) averages or smooth solutions are better than the minimum norm solution estimating the position of single point sources. However, they systematically underestimate their amplitude or strength especially for the deeper brain areas. Based on these result, it appears unlikely that a three-dimensional (3-D) tomography of the brain electromagnetic activity can be based on linear reconstruction methods without the use of a significant amount of a priori information.
Epidemiologic data and pathogen genome sequences: a powerful synergy for public health (2014)

Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional 'line lists' (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.
A Common Allele on Chromosome 9 Associated with Coronary Heart Disease (2007)

Coronary heart disease (CHD) is a major cause of death in Western countries. We used genome-wide association scanning to identify a 58-kilobase interval on chromosome 9p21 that was consistently associated with CHD in six independent samples (more than 23,000 participants) from four Caucasian populations. This interval, which is located near the CDKN2A and CDKN2B genes, contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension, or diabetes. Homozygotes for the risk allele make up 20 to 25% of Caucasians and have a approximately 30 to 40% increased risk of CHD.
Acid tolerance, proton permeabilities, and membrane ATPases of oral streptococci (1986)

Differences in acid tolerance among representative oral streptococci were found to be related more closely to the dynamic permeabilities of the bacteria to protons than to differences in the sensitivities of cell membranes to gross damage caused by environmental acidification. For Streptococcus mutans GS-5, Streptococcus sanguis NCTC 10904, and Streptococcus salivarius ATCC 13419, gross membrane damage, indicated by the release of magnesium from whole cells, occurred at pH values below about 4 and was rapid and extensive at pH values of about 3 or less. A more aciduric, lactic acid bacterium, Lactobacillus casei ATCC 4646, was more resistant to environmental acidification, and gross membrane damage was evident only at pH values below 3. Assessments of the movements of protons into S. mutans cells after an acid pulse at various pH values indicated that permeability to protons was minimal at a pH value of about 5, at which the average half time for pH equilibration across the cell membrane was about 12 min. The corresponding values for the less aciduric organism S. sanguis were pH 7 and 8.2 min, and the values for the intermediate organism S. salivarius were pH 6 and 6.6 min. The ATPase inhibitor dicyclohexylcarbodiimide acted to increase markedly the permeability of each organism to protons, and this action indicated that permeability involved not only the passive inflow of protons but also active outflow through the proton-translocating membrane ATPase. Membranes were isolated from each of the bacteria, and pH profiles for ATPase activities indicated pH optima of about 7.5, 7.0, 6.0, and 5.0 for S. sanguis, S. salivarius, S. mutans, and L. casei, respectively. Thus, the pH profiles for the enzymes reflected the acid tolerances of the bacteria and the permeabilities of whole cells to protons.
A DNA polymerase alpha pause site is a hot spot for nucleotide misinsertion. (1992)

In this study we examined whether the arrest of DNA polymerase alpha (pol alpha)-catalyzed DNA synthesis at template pause sites entails terminal nucleotide misincorporation. An approach was developed to identify the 3'-terminal nucleotide in nascent DNA chains that accumulate at pause sites. A radioactive 5'-end-labeled primer was annealed to a bacteriophage M13mp2 single-stranded DNA template and elongated by pol alpha. Individual DNA chains that were accumulated at pause sites were resolved by sequencing gel electrophoresis, isolated, and purified. These DNA chains were elongated by pol alpha by using four annealed synthetic DNA templates, each of which contained a different nucleotide at the position opposite the 3' terminus of the arrested chain. Owing to the high preference of pol alpha for matched-over-mismatched primer termini, only those templates that contain a nucleotide that is complementary to the 3' terminus of the isolated pause-site chain are copied. Electrophoresis of product DNA showed the extent of copying of each template and thus identified the 3'-terminal nucleotide of the pause-site chains. We found that product DNA chains terminate with a noncomplementary 3'-terminal nucleotide opposite pause sites within the sequence 3'-d(AAAA)-5' at positions 6272-6269 of the M13mp2 genome. pol alpha catalyzed misincorporation of dG or dA into the 3' terminus of nascent chains opposite two of the M13mp2 template dA residues. A similar analysis of a different pause site did not reveal significant misincorporation opposite template dC. These results suggest that some but not all sites at which pol alpha pauses may constitute loci of mutagenesis.
Rheological study of foam fracturing fluids using nitrogen and carbon dioxide (1983)

Foams are being used in a number of Petroleum Industry applications which exploit their high viscosity and low liquid content. Some of the earliest applications for foam dealt with its use as a displacing agent in porous media and as a drilling fluid. Following these early applications, foam was introduced as a well-bore circulating fluid for clean-out and workover applications. In the mid-1970s, nitrogen based foams became popular for both hydraulic fracturing and fracture acidizing stimulation treatments. In the latter 1970s and early 1980s foamed cementing became a viable service with foamed gravel packing close behind. Most recently, carbon dioxide foams have been found to be exhibiting their usefulness in hydraulic fracturing stimulation. This study proposes models to describe both laminar and turbulent non-Newtonian flow of nitrogen and carbon dioxide based foams. These experimentally derived models should provide a means for predicting foam flow behavior in a number of industry applications. 35 references.
Pluripotent Stem Cell-Derived Gametes: Truth and (Potential) Consequences (2009)

An emerging body of data suggests that pluripotent stem cells may be able to differentiate to form eggs and sperm. We discuss the state of the science and the potential social implications and offer recommendations for addressing some of the ethical and policy issues that would be raised by the availability of stem cell-derived gametes.
Polyhedral oligomeric silsesquioxanes tethered with perfluoroalkylthioether corner groups: Facile synthesis and enhancement of hydrophobicity of their polymer blends (2009)

Octa(vinyl)-POSS or octa(vinyldimethylsilyloxy)-POSS reacts with perfluoroalkyl thiol in the presence of 2,2′-azobisisobutyronitrile to afford perfluoroalkylthioether substituted POSS compounds in high yields. 29Si NMR and MALDI-TOF mass spectroscopic analyses indicate that the eight perfluoroalkylthioether chains are attached to the POSS core structure. Studies on poly(methyl methacrylate) (PMMA) blends with 5 wt% fluorinated POSS (fluoroPOSS) reveal that the POSS molecules considerably enhance the hydrophobicity of polymer blend surfaces as evidenced by significant increases in water contact angles from 71° for pure PMMA to 114–124° for fluoroPOSS-blends, making this type of fluoroPOSS a promising new class of highly hydrophobic hybrid materials.
Nerve Growth Factor, But Not Epidermal Growth Factor, Increases Fra-2 Expression and Alters Fra-2/JunD Binding to AP-1 and CREB Binding Elements in Pheochromocytoma (PC12) Cells (2001)

In pheochromocytoma (PC12) cells nerve growth factor (NGF) and epidermal growth factor (EGF) activate similar receptor tyrosine kinase signaling pathways but evoke strikingly different biological outcomes: NGF induces differentiation and EGF acts as a mitogen. A novel approach was developed for identifying transcription factor activities associated with NGF-activated, but not EGF-activated, signaling, using random oligonucleotide clones from a DNA recognition library to isolate specific DNA binding proteins from PC12 nuclear extracts. A protein complex from NGF-treated, but not EGF-treated, cells was identified that exhibits increased mobility and DNA binding activity in gel mobility shift assays. The binding complex was identified in supershift assays as Fra-2/JunD. The clones used as probes contain either AP-1 or cAMP response element binding (CREB) recognition elements. Time course experiments revealed further differences in NGF and EGF signaling in PC12 cells. NGF elicits a more delayed and sustained ERK phosphorylation than EGF, consistent with previous reports. Both growth factors transiently induce c-fos, but NGF evokes a greater response than EGF. NGF specifically increases Fra-1 and Fra-2 levels at 4 and 24 hr. The latter is represented in Western blots by bands in the 40-46 kDa range. NGF, but not EGF, enhances the upper bands, corresponding to phosphorylated Fra-2. These findings suggest that prolonged alterations in Fra-2 and subsequent increases in Fra-2/JunD binding to AP-1 and CREB response elements common among many gene promoters could serve to trigger broadly an NGF-specific program of gene expression.
Sialic acid content and surface hydrophobicity of group B streptococci (1993)

The sialic acid content and the cell-surface hydrophobicity index of 40 group B streptococci (GBS) strains were assessed. GBS isolated from invasive infections (virulent strains) presented an increased level of sialic acid content (1.4%) when compared with GBS isolated from asymptomatic patients (0.53%). Treatment of GBS strain 85634 with neuraminidase resulted in a decrease (about 25%) in the net negative surface charge as assessed by cell electrophoresis. This finding suggests that sialic acid residues are important anionogenic groups exposed on GBS cell surface. N-acetylneuraminic acid was the only sialic acid derivative characterized in the strain 85634 as evaluated by gas-liquid chromatography. GBS from different serotypes presented a hydrophobic index mean value of 0.9. Even though the sialic acid contributed effectively to the negative charge on GBS cell surface, no difference was observed in the hydrophobic index when virulent and avirulent strains were compared.
Gene Expression Profiling of Sporadic Parkinson's Disease Substantia Nigra Pars Compacta Reveals Impairment of Ubiquitin-Proteasome Subunits, SKP1A, Aldehyde Dehydrogenase, and Chaperone HSC-70 (2005)

Sporadic Parkinson's disease (PD) constitutes 99% of the disorder, while the remaining 1% of the cases is of familial (genetic) origin. The mutations reported to be associated with familial PD indicate impairment in protein processing and misfolding, as is handled by the ubiquitin-proteasome system (UPS), and in mitochondrial function. For these reasons, we have recently applied, for the first time, Affymetrix oligonucleotide microarray technique in the substantia nigra pars compacta of sporadic parkinsonian patients for studying global gene expression analysis and comparison to the alterations identified in inherited PD. This study identified decreased expression of 68 genes and elevation of 69 genes. Classification into functional groups revealed that the downregulated genes are related to signal transduction, protein degradation (e.g., ubiquitin-proteasome subunits), dopaminergic transmission/metabolism, iron transport, protein modification/phosphorylation, and energy pathways/glycolysis functional classes. A major finding is the decreased expressions of 5 subunits of the UPS, SKP1A, a member of the SCF (E3) ubiquitin ligase complex, and chaperone HSC-70, which can lead to a wide impairment in the function of an entire repertoire of proteins. The upregulated genes are clustered in cell adhesion/cytoskeleton, extracellular matrix components, cell cycle, protein modification/phosphorylation, protein metabolism and transcription, and inflammation/hypoxia (e.g., key iron and oxygen sensor EGLN1) classes. The study shows, for the first time, a convergence in the pathogenic processes that are observed in hereditary (familial) and sporadic PD, where abnormal iron metabolism, oxidative stress, and aggregation of proteins occur. An additional breakthrough in this research is the identification of a number of previously unsuspected crucial gene players that are also involved in the process of neurodegeneration, which can serve as specific biomarkers for PD and novel drug development.
Optimization of Thin, Nitrogen-Rich Silicon Oxynitrides Grown by Rapid Thermal Nitridation (2005)

We have systematically examined nitrogen-rich silicon oxynitrides with a thickness of about grown by rapid thermal nitridation in ammonia. In this paper the nitrogen incorporation as well as the electrical properties of the oxynitrides are discussed in detail. With the help of elastic recoil detection measurements it could be shown that the incorporated nitrogen concentration can be controlled precisely in a range between 20 and 60%, which means that even pure silicon nitride can be thermally grown in ammonia. Depending on the process flow it is also possible to adjust the nitrogen and oxygen profiles across the dielectrics depth. Regarding the electrical properties of the grown oxynitrides, we examined the impact of the variation of the process parameters and the impact of postnitridation anneals. It was found that the dilution of the process gas ammonia by the inert gas argon has a big impact on the quality of the dielectric. The optimized oxynitrides show leakage current densities which are significantly reduced compared to that of , but their interface quality is not sufficient for metal oxide semiconductor (MOS) applications. In order to reduce the interface state density , a short reoxidation in steam atmosphere combined with an anneal in forming gas results in oxynitrides with values of . It is shown that for an equivalent oxide thickness of 1.3-1.5 nm, the leakage current densities are four orders of magnitude below that of with the same thickness. Promising measurements of the effective electron mobility show that the presented oxynitrides are suitable as gate dielectrics in MOS applications in spite of the high nitrogen concentration of more than 25%.
Tissue factor-factor VIIa–specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration (2004)

Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 mRNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene is responsible for increased expression of IL-8 in FVIIa-treated cells. PAR-2-specific antibodies fully attenuated TF-FVIIa-induced IL-8 expression. Additional in vitro experiments showed that TF-FVIIa promoted tumor cell migration and invasion, active site-inactivated FVIIa, and specific antibodies against TF, PAR-2, and IL-8 inhibited TF-FVIIa-induced cell migration. In summary, the studies described herein provide insight into how TF may contribute to tumor invasion.
HEMODYNAMIC AND METABOLIC EFFECTS OF HYDROGEN SULFIDE DURING PORCINE ISCHEMIA/REPERFUSION INJURY (2008)

In awake spontaneously breathing mice, inhaling gaseous hydrogen sulfide (H2S) produced a "suspended animation-like" metabolic status with hypothermia and reduced O2 demand, thus protecting from lethal hypoxia. Murine models may be questioned, however, because due to their large surface area/mass ratio, rodents can rapidly drop their core temperature. Therefore, we investigated whether intravenous H2S (Na2S, sodium sulfide) would induce a comparable metabolic response in anesthetized and mechanically ventilated pigs. Because H2S was reported to improve heart function after myocardial ischemia, we also investigated whether sulfide would influence the noradrenaline responsiveness during reperfusion after aortic occlusion. After 2 h of i.v. sulfide (0.2 mg.kg followed by 2 mg.kg.per h; n=8) or vehicle (n=8), animals underwent 30 minutes of aortic occlusion with nitroglycerine, esmolol, and adenosine-5'-triphosphate adjusted to maintain MAP at 80% to 120% of baseline. During reperfusion, noradrenaline was titrated to keep MAP greater than or equal to 80% of this level. Sulfide reduced heart rate and cardiac output without affecting stroke volume, markedly decreased the time and dose of noradrenaline required to maintain hemodynamic targets, and caused a drop in core temperature concomitant with lower O2 uptake and CO2 production. Although arterial PCO2 and acid-base status were comparable, arterial PO2 was lower in the sulfide group at the end of the experiment. Sulfide attenuated the reperfusion-related hyperlactatemia, although glycemia was higher at the end of the experiment. The parameters of inflammation and oxidative stress did not differ. Intravenous sulfide allowed reducing energy expenditure in an anesthetized large-animal model and improved the noradrenaline responsiveness during reperfusion after aortic occlusion. Investigations are warranted, hence, whether it may also protect other organs after I/R injury.
Avelumab (MSB0010718C; anti-PD-L1) as a first-line treatment for patients with advanced NSCLC from the JAVELIN Solid Tumor phase 1b trial: Safety, clinical activity, and PD-L1 expression. (2016)

9036 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab as 1st-line therapy in patients (pts) with non-small-cell lung cancer (NSCLC) from a phase 1b trial (NCT01772004). Methods: Pts with advanced NSCLC not previously treated systemically for metastatic or recurrent disease, without an activating EGFR mutation or ALK rearrangement, and not selected for PD-L1 expression were treated with avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Responses were evaluated every 6 wks (RECIST 1.1). Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by IHC. Results: As of Oct 23, 2015, 145 pts received avelumab (median 10 wks [range 2-30]) and were followed for a median duration of 13 wks (range 0-31). Median age was 70 y (range 41-90), ECOG PS was 0 (31.0%) or 1 (69.0%), and histology was adenocarcinoma (63.4%), squamous (26.9%), other (3.4%), or unknown (6.2%). Treatment-related (TR) AEs occurred in 82 pts (56.6%; all grades); those occurring ≥ 10% were infusion-related reaction (IRR; 24 [16.6%]) and fatigue (21 [14.5%]). Grade ≥ 3 TRAEs were reported in 13 pts (9.0%); only IRR and fatigue occurred in > 1 pt (each 3 [2.1%]). There were no treatment-related deaths. Among 75 pts with ≥ 3 mos f/u, unconfirmed ORR was 18.7% (95% CI: 10.6, 29.3) based on 1 CR and 13 PRs; 12 were ongoing. Stable disease was reported in 34 pts (45.3%); disease control rate was 64.0%. PD-L1 expression was evaluable in 45/75 pts (60.0%). Based on a ≥ 1% cutoff for tumor cell staining, 35/45 (77.8%) were PD-L1+ and ORR was 20.0% in PD-L1+ (7/35; 95% CI: 8.4, 36.9) vs 0/10 (0.0, 30.8) in PD-L1– pts. Median PFS was 11.6 wks (95% CI: 6.7, 17.9) for all treated pts. Conclusions: Single-agent avelumab showed an acceptable safety profile and clinical activity in pts with NSCLC who were EGFR-wildtype and ALK-negative, not previously treated for advanced disease, and unselected for PD-L1 expression. A trend of higher ORR in PD-L1+ tumors is suggested. Phase 3 trials of avelumab in NSCLC are ongoing. *Proposed INN. Clinical trial information: NCT01772004.