gebhart/patrepeval huggingface dataset:
Structural Biology in Vaccine Research (2015)

A thorough and up-to-date review of vaccinology research in age of omics technologies. Part I covers the key innovations that are dramatically changing the field. In Part II chapters are focused on vaccines for diseases for which current treatment is ineffective. Essential reading for everyone working in vaccine R and D.
Tuning the optical response of a dimer nanoantenna using plasmonic nanoring loads (2015)

The optical properties of a dimer type nanoantenna loaded with a plasmonic nanoring are investigated through numerical simulations and measurements of fabricated prototypes. It is demonstrated that by judiciously choosing the nanoring geometry it is possible to engineer its electromagnetic properties and thus devise an effective wavelength dependent nanoswitch. The latter provides a mechanism for controlling the coupling between the dimer particles, and in particular to establish a pair of coupled/de-coupled states for the total structure, that effectively results in its dual mode response. Using electron beam lithography the targeted structure has been accurately fabricated and the desired dual mode response of the nanoantenna was experimentally verified. The response of the fabricated structure is further analyzed numerically. This permits the visualization of the electromagnetic fields and polarization surface charge distributions when the structure is at resonance. In this way the switching properties of the plasmonic nanoring are revealed. The documented analysis illustrates the inherent tuning capabilities that plasmonic nanorings offer, and furthermore paves the way towards a practical implementation of tunable optical nanoantennas. Additionally, our analysis through an effective medium approach introduces the nanoring as a compact and efficient solution for realizing nanoscale circuits.
Guaiac Testing in the Diagnosis of Rectal Trauma (1992)

Rectal examination with guaiac testing is a standard part of the emergency department evaluation of acutely traumatized patients. Its major role is in the recognition of occult bowel injury. We questioned its efficacy in detecting occult rectal injury in patients with penetrating trauma. We reviewed the charts of 19 patients with suspected rectal injury. Ten injuries were to the abdomen, nine to the buttock, and three to the thigh. Guaiac testing was 69% (11/16) sensitive and 33% (1/3) specific. Rigid sigmoidoscopy was 100% (12/12) sensitive and 67% (2/3) specific. Sensitivity was 100% (8/8) when the two were combined. Our findings suggest that guaiac testing is not accurate enough to rule out the presence of occult rectal injury. The result of guaiac testing must not influence the decision to further evaluate patients with high-risk injuries.
Role of protein kinase c and cytokines on the function and production of cytolytic granules in αCD3‐activated killer‐cell‐mediated killing of tumor cells (1993)

The effects of PMA and staurosporine (PKC depletor/antagonist) and IL-2/IL4 were used to determine the role of PKC and cytokine on alpha CD3-induced activated killer cells (CD3-AK). The present study examines their effects on the production of BLT-esterase and on the effector function of CD3-AK cells as well as the cytolytic granules. The production of BLT-esterase generally correlated with the cytolytic activity of CD3-AK cells and was reduced by PKC depletor/inhibitor but increased by IL-4. In studying the effector function of CD3-AK cells, we found that adding PMA or SSP at the effector phase inhibited the PKC-dependent slow lysis. PMA, but not SSP, also reduced fast lysis, which was shown to be a PKC-independent event. Additional experiments were performed to determine the effect of PKC on the lytic granules and to ascertain whether PMA has other effects on the effector-to-target relationship unrelated to PKC. It was found that neither PMA nor SSP affects the function of cytolytic granules, as measured by hemolytic assay against anucleated target (SRBC). These findings indicate that PKC has no direct effect on the granules. During testing against the nucleated tumor target through a novel approach using non-cytolytic surrogate killers, the lytic activity of the granules was inhibited by PMA, suggesting that exocytosis or delivery of granules to nucleated target cells may require mobilization of intracellular Ca2+ in the killer cells, and this process is inhibited by PMA. Our findings indicate that PKC and cytokines regulate the production but not the lytic activity of cytolytic granules. Nonetheless, delivery of cytolytic granules from killer cells to the nucleated tumor target appears to be a Ca(2+)-dependent event unrelated to PKC.
Effect of cell proliferation and chromatin conformation on intercalator-induced, protein-associated DNA cleavage in human brain tumor cells and human fibroblasts. (1987)

Antineoplastic intercalating agents such as 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) stabilize a cleavable complex between topoisomerase II and DNA. The production of protein-associated DNA cleavage in whole cells exposed to m-AMSA is thought to represent the cellular correlate of this topoisomerase II-mediated reaction. Protein-associated DNA cleavage can be quantified in mammalian cells by using alkaline elution technology. In an attempt to understand the impact of phenotypic and biochemical cellular characteristics on protein-associated DNA cleavage, we quantified m-AMSA-induced DNA cleavage in quiescent or proliferative normal human fibroblasts (cell strain 1508) and human glioblastoma cells (line T98G) as well as in asynchronously proliferating HeLa cells. The magnitude of DNA cleavage in quiescent fibroblasts and quiescent glioblastoma cells was identical and low relative to that observed in the HeLa cells. The magnitude of DNA cleavage was enhanced in both cell types following proliferation. This enhancement was greater in the glioblastoma cells than in the fibroblasts. These results were not due to alterations in cellular m-AMSA uptake. Chromatin was more elongated (open) in the quiescent glioblastoma cells than in the quiescent fibroblasts (as visualized by using the premature chromosome condensation assay), suggesting chromatin accessibility to drug per se may not be a critical determinant of the magnitude of m-AMSA-induced DNA cleavage. The onset of the enhanced m-AMSA-induced DNA cleavability that accompanied proliferation closely followed the formation of regions of localized chromatin decondensation, a late G1 event, and coincided with the onset of enhanced thymidine uptake, a marker for the onset of S phase. m-AMSA-induced cytotoxicity was also enhanced in proliferating compared with quiescent cells. The major finding of this study is that the cellular target for m-AMSA, putatively topoisomerase II, is more susceptible to drug action in proliferating cells than in quiescent cells. Effects of chromatin conformation or cellular phenotype upon topoisomerase II-mediated events such as m-AMSA-induced DNA cleavage are less certain.
High rates of chromosome missegregation suppress tumor progression but do not inhibit tumor initiation (2016)

Aneuploidy, an abnormal chromosome number that deviates from a multiple of the haploid, has been recognized as a common feature of cancers for >100 yr. Previously, we showed that the rate of chromosome missegregation/chromosomal instability (CIN) determines the effect of aneuploidy on tumors; whereas low rates of CIN are weakly tumor promoting, higher rates of CIN cause cell death and tumor suppression. However, whether high CIN inhibits tumor initiation or suppresses the growth and progression of already initiated tumors remained unclear. We tested this using the Apc(Min/+) mouse intestinal tumor model, in which effects on tumor initiation versus progression can be discriminated. Apc(Min/+) cells exhibit low CIN, and we generated high CIN by reducing expression of the kinesin-like mitotic motor protein CENP-E. CENP-E(+/-);Apc(Min/+) doubly heterozygous cells had higher rates of chromosome missegregation than singly heterozygous cells, resulting in increased cell death and a substantial reduction in tumor progression compared with Apc(Min/+) animals. Intestinal organoid studies confirmed that high CIN does not inhibit tumor cell initiation but does inhibit subsequent cell growth. These findings support the conclusion that increasing the rate of chromosome missegregation could serve as a successful chemotherapeutic strategy.
Pyrolysis of C[sub 60]-thin films yields Ni-filled sharp nanotubes (1998)

Highly graphitised needle-like elongated carbon nanostructures containing encapsulated Ni, are produced by heating alternating thin films of C60 and Ni on a silica plate at 950 °C. High Resolution Transmission Electron Microscopy (HRTEM) studies reveal that these tapering structures are fully filled with Ni and are closed at both ends. The diameters of the needles (ca. 2–5 μm in length) range between 10–20 nm at one end and 30–200 nm at the other. A surprisingly high degree of graphitisation was observed for the nanostructures. They may prove to be useful as Scanning Tunnelling Microscope (STM) tips due to their shape.
High-speed asynchronous optical sampling with sub-50fs time resolution (2010)

We report an ultrafast time-domain spectroscopy system based on high-speed asynchronous optical sampling operating without mechanical scanner. The system uses two 1 GHz femtosecond oscillators that are offset-stabilized using high-bandwidth feedback electronics operating at the tenth repetition rate harmonics. Definition of the offset frequency, i.e. the time-delay scan rate, in the range of a few kilohertz is accomplished using direct-digital-synthesis electronics for the first time. The time-resolution of the system over the full available 1 ns time-delay window is determined by the laser pulse duration and is 45 fs. This represents a three-fold improvement compared to previous approaches where timing jitter was the limiting factor. Two showcase experiments are presented to verify the high time-resolution and sensitivity of the system.
GLDPC-Staircase AL-FEC codes: a fundamental study and new results (2016)

This paper provides fundamentals in the design and analysis of Generalized Low-Density Parity Check (GLDPC)-Staircase codes over the erasure channel. These codes are constructed by extending an LDPC-Staircase code (base code) using Reed-Solomon (RS) codes (outer codes) in order to benefit from more powerful decoders. The GLDPC-Staircase coding scheme adds, in addition to the LDPC-Staircase repair symbols, extra-repair symbols that can be produced on demand and in large quantities, which provides small rate capabilities. Therefore, these codes are extremely flexible as they can be tuned to behave either like predefined rate LDPC-Staircase codes at one extreme, or like a single RS code at another extreme, or like small rate codes. Concerning the code design, we show that RS codes with “quasi” Hankel matrix-based construction fulfill the desired structure properties, and that a hybrid (IT/RS/ML) decoding is feasible that achieves maximum likelihood (ML) correction capabilities at a lower complexity. Concerning performance analysis, we detail an asymptotic analysis method based on density evolution (DE), extrinsic information transfer (EXIT), and the area theorem. Based on several asymptotic and finite length results, after selecting the optimal internal parameters, we demonstrate that GLDPC-Staircase codes feature excellent erasure recovery capabilities, close to that of ideal codes, both with large and very small objects. From this point of view, they outperform LDPC-Staircase and Raptor codes and achieve correction capabilities close to those of RaptorQ codes. Therefore, all these results make GLDPC-Staircase codes a universal Application-Layer FEC (AL-FEC) solution for many situations that require erasure protection such as media streaming or file multicast transmission.
The biological significance of histone modifiers in multiple myeloma: clinical applications (2018)

Multiple myeloma (MM) is a clonal plasma cell disorder that is characterized by a variety of genetic alterations. Recent studies have highlighted not only the importance of these genetic events but also epigenetic aberrations including DNA methylation, histone modifications, and non-coding RNAs in the biology of MM. Post-translational modifications of histone, such as methylation and acetylation, contribute to chromatin dynamics, and are modulated by histone modifying enzymes, and dysregulation of these enzymes is implicated in the pathogenesis of cancers, including MM. Histone modifiers also have non-histone substrates and enzymatically independent roles, which are also involved in tumorigenesis. Here we review and provide comprehensive insight into the biologic significance of histone methyl- and acetyl-modifiers in MM, and further provide an overview of the clinical applications of histone modifier inhibitors, especially histone deacetylase inhibitors. These findings underline the emerging roles of histone modifiers in the pathogenesis of MM, and further highlight the possibility of novel epigenetic therapies in MM.
Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease (2005)

CSF total homocysteine is not increased in Alzheimer's disease compared with age matched controls. CSF total homocysteine was correlated with age. The decrease in CSF MMA levels with age eliminates a lack of vitamin B-12 at neuronal level.
Antiretroviral Therapy with Protease Inhibitors Has an Early, Immune Reconstitution–Independent Beneficial Effect on<i>Candida</i>Virulence and Oral Candidiasis in Human Immunodeficiency Virus–Infected Subjects (2002)

Highly active antiretroviral therapies (HAARTs) that contain human immunodeficiency virus (HIV) protease inhibitors (PIs) or nonnucleoside reverse-transcriptase inhibitors (NNRTIs) were compared for their effect on secretory aspartyl proteinase (Sap), a virulence trait for mucosal candidiasis. In therapy-naive HIV-positive subjects, oral Sap was detected in 11, 6, 3, 0, and 0 of 15 subjects treated with PI-HAART and in 7, 7, 9, 6, and 5 of 15 subjects treated with NNRTI-HAART, on days 0, 14, 30, 90, and 180 of treatment, respectively. In another 30 subjects, Sap was detected in 0 and 7 of 15 subjects after 1 year of treatment with PI-HAART or NNRTI-HAART, respectively. The anti-Sap effect of PI-HAART was associated with clinical resolution of oral candidiasis but not with late and inconstant recovery of anticandidal cellular immunity. In all subjects, the 2 therapeutic regimens compared well in increasing CD4(+) cell count and abating viremia. Thus, PIs exert an early, immune reconstitution-independent effect on Candida virulence in the oral cavities of HIV-positive subjects.
Incus Necrosis and Blood Supply: A Micro-CT and Synchrotron Imaging Study (2019)

SR-PCI with 3D reconstructions confirmed the main vascular supply to the lenticular process along the intraosseous lenticular vessels. This is the first synchrotron analysis of a patient having undergone stapes surgery, and it suggests that incus necrosis associated with stapes surgery may be caused by a disruption of the lenticular blood flow induced by the prosthesis loop, and not by strangulation of mucosal vessels as has been previously described.
Microsatellite analysis of environmental and clinical isolates of the opportunist fungal pathogen Aspergillus fumigatus (2002)

Microsatellite analysis was used to examine the genetic relatedness of 111 clinical and environmental isolates of the opportunist human pathogenic fungus Aspergillus fumigatus from Ontario, Canada. Forty-three A. fumigatus isolates were from clinical sources and 68 from environmental sources. Phylogenetic analysis of the genotypes revealed that there were no geographical or temporal associations of clinical or environmental genotypes. In fact, several of the environmental and clinical isolates showed identical (clonal) genotypes from disparate geographical areas. However, a locus by locus examination revealed that there were several significant differences in allele frequencies between clinical and environmental isolates. There may be linkage of certain microsatellite loci with genes affecting virulence in A. fumigatus. A susceptible individual may be equally predisposed to infection by any isolate of A. fumigatus. However, under transient selection as a pathogen, genes encoding alleles for enhanced virulence may not assort independently from microsatellite loci. A dynamic equilibrium may exist between random recombination of loci in the natural environment and selection for virulence factors during host infection cycles.
Response—Energy Strategies and Efficiency (2009)

Briggs argues that energy strategies should not focus exclusively on efficiency. We agree and explicitly state a wide range of criteria in our Report. Briggs also argues that biomass should be dedicated to liquid fuel production to allow for a complete transition away from fossil fuels, whereas
SUPER-RESOLUTION FROM A LOW- AND PARTIAL HIGH- RESOLUTION IMAGE PAIR (2014)

The classical super-resolution (SR) setting starts with a set of low-resolution (LR) images related by subpixel shifts and tries to reconstruct a single high-resolution (HR) image. In some cases, partial observations about the HR image are also available. Trying to complete the missing HR data without any reference to LR ones is an inpainting (or completion) problem. In this paper, we consider the problem of recov- ering a single HR image from a pair consisting of a complete LR and incomplete HR image pair. This setting arises in par- ticular when one wants to fuse image data captured at two different resolutions. We propose an efficient algorithm that allows to take advantage of both image data by first learning nonlocal interactions from an interpolated version of the LR image using patches. Those interactions are then used by a convex energy function whose minimization yields a super- resolved complete image.
Saposin-like proteins from the intestine of the blood-feeding hookworm, <i>Ancylostoma caninum</i> (2006)

Hookworms feed on blood, utilizing haemoglobin for nutrition, growth and reproduction. The haemoglobin digestion cascade has been partially elucidated, but the process immediately preceding this event, haemolysis, has received considerably less attention. We have cloned and expressed Ancylostoma caninum mRNAs encoding 2 proteins belonging to the saposin-like protein (SAPLIP) family, termed Ac-slp-1 and Ac-slp-2. The open reading frames of SLP-1 and SLP-2 were used to identify expressed sequence tags encoding SAPLIPs from the 4 major clades of animal parasitic nematodes. Both Ac-slp-1 and slp-2 mRNAs were shown to be expressed in all life stages assessed, with slp-1 predominantly being expressed in third-stage larvae (L3) before and after activation with dog serum. Recombinant SLP-1 and SLP-2 were expressed in insect cells and used to raise specific antisera in mice. These antisera were used as probes in fluorescence microscopy to localize the anatomic expression sites of both proteins to small, punctate organelles or vesicles within the intestinal cells of adult worms; weak staining was detected on the microvillar brush border of the intestine. Using transmission electron microscopy, both proteins were localized to similar vesicles in the intestinal cells of the L3. Recombinant proteins contained C-terminal purification tags that potentially precluded dimerization and possibly interfered with the subsequent detection of haemolytic activity. Their expression in the gut of the L3 and adult stages suggests a role for these hookworm SAPLIPs in the lysis of host cells during tissue migration and/or feeding.
Targeted Maximum Likelihood Estimation for Dynamic and Static Longitudinal Marginal Structural Working Models (2014)

This paper describes a targeted maximum likelihood estimator (TMLE) for the parameters of longitudinal static and dynamic marginal structural models. We consider a longitudinal data structure consisting of baseline covariates, time-dependent intervention nodes, intermediate time-dependent covariates, and a possibly time-dependent outcome. The intervention nodes at each time point can include a binary treatment as well as a right-censoring indicator. Given a class of dynamic or static interventions, a marginal structural model is used to model the mean of the intervention-specific counterfactual outcome as a function of the intervention, time point, and possibly a subset of baseline covariates. Because the true shape of this function is rarely known, the marginal structural model is used as a working model. The causal quantity of interest is defined as the projection of the true function onto this working model. Iterated conditional expectation double robust estimators for marginal structural model parameters were previously proposed by Robins (2000, 2002) and Bang and Robins (2005). Here we build on this work and present a pooled TMLE for the parameters of marginal structural working models. We compare this pooled estimator to a stratified TMLE (Schnitzer et al. 2014) that is based on estimating the intervention-specific mean separately for each intervention of interest. The performance of the pooled TMLE is compared to the performance of the stratified TMLE and the performance of inverse probability weighted (IPW) estimators using simulations. Concepts are illustrated using an example in which the aim is to estimate the causal effect of delayed switch following immunological failure of first line antiretroviral therapy among HIV-infected patients. Data from the International Epidemiological Databases to Evaluate AIDS, Southern Africa are analyzed to investigate this question using both TML and IPW estimators. Our results demonstrate practical advantages of the pooled TMLE over an IPW estimator for working marginal structural models for survival, as well as cases in which the pooled TMLE is superior to its stratified counterpart.
Humoral and cellular immune response to a crude exo-antigen and purified keratinase of<i>Microsporum canis</i>in experimentally infected guinea pigs (1999)

In order to understand better the host-parasite relationship and to compare with previous observations in Microsporum canis naturally infected cats, the humoral and cellular immune responses to both a crude exo-antigen and a 31·5 kDa purified keratinase were evaluated in 12 M. canis experimentally infected guinea pigs. Humoral and cellular responses were assessed by ELISA from days 0 to 56 postinfection (PI) and by measurement of delayed-type hypersensitivity (DTH) responses on days 14 and 57 PI, respectively. Additionally, immunohistochemical staining was performed and demonstrated that the keratinase was produced in infected guinea pig skin, as previously reported in cats. Despite a marked interindividual variation, all the guinea pigs produced specific IgG to the crudeexo-antigen from day 21 PI onwards, but no anti-keratinase IgG was detected. Strongly positive DTH responses to the exo-antigen were observed on both dates, whereas the keratinase elicited no and weak DTH on days 14 and 57 PI, respectively. These results are in agreement with thosepreviously described for naturally infected cats, and indicate that the 31·5 kDa keratinase is not a major antigen in M. canis infection.