gebhart/patrepeval huggingface dataset:
Crystal Structure of the HNF4α Ligand Binding Domain in Complex with Endogenous Fatty Acid Ligand (2002)

HNF4 alpha is an orphan member of the nuclear receptor family with prominent functions in liver, gut, kidney and pancreatic beta cells. We have solved the x-ray crystal structure of the HNF4 alpha ligand binding domain, which adopts a canonical fold. Two conformational states are present within each homodimer: an open form with alpha helix 12 (alpha 12) extended and collinear with alpha 10 and a closed form with alpha 12 folded against the body of the domain. Although the protein was crystallized without added ligands, the ligand binding pockets of both closed and open forms contain fatty acids. The carboxylic acid headgroup of the fatty acid ion pairs with the guanidinium group of Arg(226) at one end of the ligand binding pocket, while the aliphatic chain fills a long, narrow channel that is lined with hydrophobic residues. These findings suggest that fatty acids are endogenous ligands for HNF4 alpha and establish a framework for understanding how HNF4 alpha activity is enhanced by ligand binding and diminished by MODY1 mutations.
Nucleases: diversity of structure, function and mechanism (2010)

Nucleases cleave the phosphodiester bonds of nucleic acids and may be endo or exo, DNase or RNase, topoisomerases, recombinases, ribozymes, or RNA splicing enzymes. In this review, I survey nuclease activities with known structures and catalytic machinery and classify them by reaction mechanism and metal-ion dependence and by their biological function ranging from DNA replication, recombination, repair, RNA maturation, processing, interference, to defense, nutrient regeneration or cell death. Several general principles emerge from this analysis. There is little correlation between catalytic mechanism and biological function. A single catalytic mechanism can be adapted in a variety of reactions and biological pathways. Conversely, a single biological process can often be accomplished by multiple tertiary and quaternary folds and by more than one catalytic mechanism. Two-metal-ion-dependent nucleases comprise the largest number of different tertiary folds and mediate the most diverse set of biological functions. Metal-ion-dependent cleavage is exclusively associated with exonucleases producing mononucleotides and endonucleases that cleave double- or single-stranded substrates in helical and base-stacked conformations. All metal-ion-independent RNases generate 2',3'-cyclic phosphate products, and all metal-ion-independent DNases form phospho-protein intermediates. I also find several previously unnoted relationships between different nucleases and shared catalytic configurations.
Novel techinque for monitoring long-haul undersea optical-amplifier systems (1994)

The next generation of long-haul undersea transmission systems will use erbium-doped fiber amplifiers (EDFAs) and will require new techniques for system monitoring. We describe experimental results showing the feasibility of passive high-loss loopbacks and digital correlation for in-service monitoring and out-of-service fault location.
Peptide-MHC Class II Dimers as Therapeutics to Modulate Antigen-Specific T Cell Responses in Autoimmune Diabetes (2003)

Type 1 diabetes is an autoimmune disorder caused by autoreactive T cells that mediate destruction of insulin-producing beta cells of the pancreas. Studies have shown that T cell tolerance can be restored by inducing a partial or altered signal through the TCR. To investigate the potential of bivalent peptide-MHC class II/Ig fusion proteins as therapeutics to restore Ag-specific tolerance, we have developed soluble peptide I-A(g7) dimers for use in the nonobese diabetic mouse model of diabetes. I-A(g7) dimers with a linked peptide specific for islet-reactive BDC2.5 TCR transgenic CD4(+) T cells were shown to specifically bind BDC2.5 T cells as well as a small population of Ag-specific T cells in nonobese diabetic mice. In vivo treatment with BDC2.5 peptide I-A(g7) dimers protected mice from diabetes mediated by the adoptive transfer of diabetogenic BDC2.5 CD4(+) T cells. The dimer therapy resulted in the activation and increased cell death of transferred BDC2.5 CD4(+) T cells. Surviving cells were hypoproliferative to challenge by Ag and produced increased levels of IL-10 and decreased levels of IFN-gamma compared with cells from control I-A(g7) dimer-treated mice. Anti-IL-10R therapy reversed the tolerogenic effects of the dimer. Thus, peptide I-A(g7) dimers induce tolerance of BDC2.5 TCR T cells through a combination of the induction of clonal anergy and anti-inflammatory cytokines.
Effect of mycolase and amphotericin B onCandida albicansandCandida pseudotropicalis in vitroandin vivo (1985)

A mixture of enzymes (mycolase) capable of lysing yeast cell walls was prepared from culture filtrates of Physarum polycephalum. The enzymes present in mycolase included chitinase, beta-1,3-glucanases and exo-glycosidases. The pH optima of these enzymes were in the range 3.5-5.0 and they had low activities at pH 7.0. Mycolase produced spheroplasts from Candida pseudotropicalis and, unlike commercial enzyme preparations such as L1, chitinase, beta, 1,3-glucanase and beta-glucosidase, had some candicidal activity in vitro against C. pseudotropicalis and C. albicans. Mycolase potentiated the antifungal activity of amphotericin B against C. pseudotropicalis grown in shake flask culture but did not potentiate the antifungal activity of the antibiotic against similar cultures of C. albicans; indeed antagonism between mycolase and amphotericin B was sometimes observed with the latter yeast. Mycolase caused an approximately two-fold increase in the total and viable counts of cultures of C. albicans inoculated with stationary phase cells. These increases, which were observed within about 30 min, were attributed to mycolase inducing the premature release of viable buds from 'lag' phase cells. Mycolase also increased the rate at which C. albicans formed germ tubes when the yeast was cultured in a medium containing serum. Mycolase alone or in combination with amphotericin B did not appreciably enhance phagocytosis or intracellular killing of the yeasts by unstimulated mouse peritoneal macrophages. Studies on mice infected systemically with C. albicans showed that mycolase only slightly enhanced amphotericin B therapy.
Effect of β radiation on success of glaucoma drainage surgery in South Africa: randomised controlled trial (2006)

ISRCTN62430622 [controlled-trials.com].
Hormonally active peptides in human milk (1994)

Human milk contains many hormone and hormone-like peptides. The gastrointestinal tract of newborn infants exhibits lower proteolytic activity than in adults and higher "permeability" for macromolecules. Studies in experimental animals demonstrate that several peptides (epidermal growth factors, insulin-like growth factor I and bombesin) after orogastric administration exhibit effects on the small intestine and other organs (liver or pancreas). Few studies performed in human neonates suggest a "survival" of epidermal growth factor in their gastric content. Further studies are needed to evaluate the role of milk-borne hormonally active peptides. This need is stressed by the fact that several of those known to be present in human milk were found to be low or not detectable in infant formulae (epidermal growth factor, insulin-like growth factor I, insulin, parathyroid hormone-related peptide.
Shooting Tourists in Cambodia (2006)

Tourists in Cambodia can visit the 'Killing Fields' or Choeung Ek Genocidal Centre, the site of Cambodia's largest mass grave, and take a trip to a near-by shooting range, which is 1km away from Choeung Ek. The shooting range provides an opportunity to fire a weapon of tourists' choice including AK47s, and hand guns, as well as grenades and heavy artillery. This side trip is vastly popular amongst backpackers. The author asserts that both historical atrocity and recreational gun use, the emotional saturation of the horror of Cheoung Ek and the 'cathartic' experience of firing a weapon, have become two sides of the same coin to the tourist seeking to 'discover' Cambodia.
Development of Calibrated Viral Load Standards for Group M Subtypes of Human Immunodeficiency Virus Type 1 and Performance of an Improved AMPLICOR HIV-1 MONITOR Test with Isolates of Diverse Subtypes (1999)

Accurate determination of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels is critical for the effective management of HIV-1 disease. The AMPLICOR HIV-1 MONITOR Test, a reverse transcription-PCR-based test for quantification of HIV-1 RNA in plasma, was developed when little sequence information on HIV-1 isolates from outside North America was available. It has since become apparent that many non-subtype B isolates, particularly subtypes A and E, are detected inefficiently by the test. We describe here the AMPLICOR HIV-1 MONITOR Test, version 1.5, an upgraded test developed to minimize subtype-related variation. We also developed a panel of HIV-1 standards containing 30 HIV-1 isolates of subtypes A through G. The virus particle concentration of each cultured viral stock was standardized by electron microscopic virus particle counting. We used this panel to determine the performance of the original AMPLICOR HIV-1 MONITOR Test and version 1.5 of the test with HIV-1 subtypes A through G. The original test underestimated the concentration of HIV-1 subtype A, E, F, and G RNA by 10-fold or more, whereas version of the 1.5 test yielded equivalent quantification of HIV-1 RNA regardless of the subtype. In light of the increasing intermixing of HIV-1 subtypes worldwide, standardization of PCR-based tests against well-characterized viral isolates representing the full range of HIV-1 diversity will be essential for the continued utility of these important clinical management tools.
A Robust Physical Unclonable Function With Enhanced Challenge-Response Set (2011)

A Physical Unclonable Function (PUF) is a promising solution to many security issues due its ability to generate a die unique identifier that can resist cloning attempts as well as physical tampering. However, the efficiency of a PUF depends on its implementation cost, its reliability, its resiliency to attacks, and the amount of entropy in it. PUF entropy is used to construct crypto graphic keys, chip identifiers, or challenge-response pairs (CRPs) in a chip authentication mechanism. The amount of entropy in a PUF is limited by the circuit resources available to build a PUF. As a result, generating longer keys or larger sets of CRPs may increase PUF circuit cost. We address this limitation in a PUF by proposing an identity-mapping function that expands the set of CRPs of a ring-oscillator PUF (RO-PUF) with low area cost. The CRPs generated through this function exhibit strong PUF qualities in terms of uniqueness and reliability. To introduce the identity-mapping function, we formulate a novel PUF system model that uncouples PUF measurement from PUF identifier formation. We show the enhanced CRP generation capability of the new function using a statistical hypothesis test. An implementation of our technique on a low-cost FPGA platform shows at least 2 times savings in area compared to the traditional RO-PUF. The proposed technique is validated using a population of 125 chips, and its reliability over varying environmental conditions is shown.
ICOS Controls the Pool Size of Effector-Memory and Regulatory T Cells (2008)

ICOS is an important regulator of T cell effector function. ICOS-deficient patients as well as knockout mice show severe defects in T cell-dependent B cell responses. Several in vitro and in vivo studies attributed this phenomenon to impaired up-regulation of cell surface communication molecules and cytokine synthesis by ICOS-deficient T cells. However, we now could show with Ag-specific T cells in a murine adoptive transfer system that signaling via ICOS does not significantly affect early T cell activation. Instead, ICOS substantially contributes to the survival and expansion of effector T cells upon local challenge with Ag and adjuvant. Importantly, the observed biological function of ICOS also extends to FoxP3+ regulatory T cells, as can be observed after systemic Ag delivery without adjuvant. In line with these findings, absence of ICOS under homeostatic conditions of nonimmunized mice leads to a reduced number of both effector-memory and FoxP3+ regulatory T cells. Based on these results, we propose a biological role for ICOS as a costimulatory, agonistic molecule for a variety of effector T cells with differing and partly opposing functional roles. This concept may reconcile a number of past in vivo studies with seemingly contradictory results on ICOS function.
Application of Mie theory to assess structure of spheroidal scattering in backscattering geometries (2008)

Inverse light scattering analysis seeks to associate measured scattering properties with the most probable theoretical scattering distribution. Although Mie theory is a spherical scattering model, it has been used successfully for discerning the geometry of spheroidal scatterers. The goal of this study was an in-depth evaluation of the consequences of analyzing the structure of spheroidal geometries, which are relevant to cell and tissue studies in biology, by employing Mie-theory-based inverse light scattering analysis. As a basis for this study, the scattering from spheroidal geometries was modeled using T-matrix theory and used as test data. In a previous study, we used this technique to investigate the case of spheroidal scatterers aligned with the optical axis. In the present study, we look at a broader scope which includes the effects of aspect ratio, orientation, refractive index, and incident light polarization. Over this wide range of parameters, our results indicate that this method provides a good estimate of spheroidal structure.
Selective loss of glial glutamate transporter GLT‐1 in amyotrophic lateral sclerosis (1995)

The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is unknown, but defects in synaptosomal high-affinity glutamate transport have been observed. In experimental models, chronic loss of glutamate transport can produce a loss of motor neurons and, therefore, could contribute to the disease. With the recent cloning of three glutamate transporters, i.e., EAAC1, GLT-1, and GLAST, it has become possible to determine if the loss of glutamate transport in ALS is subtype specific. We developed C-terminal, antioligopeptide antibodies that were specific for each glutamate transporter. EAAC1 is selective for neurons, while GLT-1 and GLAST are selective for astroglia. Tissue from various brain regions of ALS patients and controls were examined by immunoblot or immunocytochemical methods for each transporter subtype. All tissue was matched for age and postmortem delay. GLT-1 immunoreactive protein was severely decreased in ALS, both in motor cortex (71% decrease compared with control) and in spinal cord. In approximately a quarter of the ALS motor cortex specimens, the loss of GLT-1 protein (90% decrease from control) was dramatic. By contrast, there was only a modest loss (20% decrease from control) of immunoreactive protein EAAC1 in ALS motor cortex, and there was no appreciable change in GLAST. The minor loss of EAAC1 could be secondary to loss of cortical motor neurons. As a comparison, glial fibrillary acidic protein, which is selectively localized to astroglia, was not changed in ALS motor cortex. Because there is no loss of astroglia in ALS, the dramatic abnormalities in GLT-1 could reflect a primary defect in GLT-1 protein, a secondary loss due to down regulation, or other toxic processes.
Block copolymers as photonic bandgap materials (1999)

Block copolymers self-assemble into one-, two-, and three-dimensional periodic equilibrium structures, which can exhibit photonic bandgaps. This paper outlines a methodology for producing photonic crystals at optical length scales from block copolymers. Techniques for enhancing the intrinsic dielectric contrast between the block copolymer domains, as well as increasing the characteristic microdomain distances, and controlling defects are presented. To demonstrate the applicability of this methodology, a self-assembled one-dimensional periodic structure has been fabricated that reflects visible light. The wealth of structures into which block copolymers can assemble and the multiple degrees of freedom that can be built into these materials on the molecular level offer a large parameter space for tailoring new types of photonic crystals at optical length scales.
Bioreactors get personal (2012)

Adoptive cell transfer immunotherapy against melanoma is highly effective. However, this therapy has seen limited dissemination, mainly due to the complexity and costs of cell expansion protocols. Two bioreactors have recently been described that simplify and streamline the production of individualized cell therapies. Such bioreactors might increase the number of patients that get access to this promising therapeutic modality.
Diffusion barrier properties of transition metal thin films grown by plasma-enhanced atomic-layer deposition (2002)

Ta thin films were grown on Si(001) and polycrystalline Si substrates by plasma-enhanced atomic-layer deposition (PE-ALD) using TaCl5 and atomic hydrogen as precursors. The grown films have resistivity of 150–180 μm cm with a small Cl concentration between 0.5 and 2 at. %. The diffusion barrier properties were investigated using bilayer structures consisting of 200 nm Cu deposited by sputtering on ALD Ta films with various thicknesses. Three in situ analysis techniques consisting of x-ray diffraction, elastic light scattering, and resistance analysis were used to determine the diffusion barrier failure temperature of Ta films. The barriers were annealed at a temperature ramp rate of 3 °C/s from 100 to 1000 °C in forming gas. For this method using x-ray diffraction, the barrier failure temperatures were determined by monitoring the disappearance of the Cu(111) x-ray diffraction peak and appearance of Cu silicide diffraction peaks. At the diffusion barrier failure temperature, elastic light scattering indicated a rapid increase in surface roughness, and concurrent increases in sheet resistance of the blanket Cu/ALD Ta films on polycrystalline Si were monitored using a four-point-probe technique. The same analyses were performed on bilayer structures of Cu/physical-vapor-deposition Ta films with comparable thicknesses. The ALD Ta barrier films show significantly higher failure temperatures compared to PVD Ta; at least 70 °C at comparable thicknesses, which is thought to be due to the uniform, smooth surface and amorphous or nanocrystalline microstructure of ALD Ta.
Biodegradable polymers for controlled delivery of chemotherapy with and without radiation therapy in the monkey brain (1994)

Sustained drug delivery by biodegradable polymer devices can increase the therapeutic efficacy of drugs by producing high local tissue concentrations over extended periods of time. It has been shown previously that implantation of controlled-release polymers impregnated with the nitrosourea carmustine (BCNU) extended the period of survival in rats bearing the 9L glioma compared with similar rats treated with systemically administered BCNU. This study evaluated the effect on the monkey brain of interstitial delivery of BCNU by the biodegradable polyanhydride copolymer poly[bis(p-carboxyphenoxy)propane]anhydride (PCPP) and sebacic acid (SA) in a 20:80 formulation (PCPP:SA). The effect of combining interstitial BCNU with radiation therapy was also evaluated. Eighteen male cynomolgus monkeys were randomly assigned to one of four groups: a control group; a group with implantation of empty polymer; a group with implantation of BCNU-loaded polymer; and a group with implantation of empty polymer in the right hemisphere and BCNU-loaded polymer in the left hemisphere, followed by irradiation. The effects were evaluated radiologically and histologically at specified times. A local reaction by the brain to the polymer was found, which was greater when the polymer contained BCNU. Local cerebral edema was observed radiographically on postoperative Day 14 and had resolved by Day 72. Histologically, a subacute cellular inflammatory response was seen on postoperative Day 16, which had changed to a chronic inflammatory response by Day 72. In the group with radiation therapy administered to the hemisphere bearing BCNU-loaded polymer, only localized pathological changes were detected. In all animals, brain distant from the polymer implantation site was normal. No neurological or general deleterious effects were seen in any of the animals. It is concluded that the interstitial delivery of BCNU by the polyanhydride polymer PCPP:SA is safe in the primate brain and that concomitant radiation therapy did not lead to any adverse effects. These experimental findings are important to an understanding of the clinical effects of PCPP:SA implants in treating brain diseases.
Controlling and Switching the Morphology of Micellar Nanoparticles with Enzymes (2011)

Micelles were prepared from polymer-peptide block copolymer amphiphiles containing substrates for protein kinase A, protein phosphatase-1, and matrix metalloproteinases 2 and 9. We examine reversible switching of the morphology of these micelles through a phosphorylation-dephosphorylation cycle and study peptide-sequence directed changes in morphology in response to proteolysis. Furthermore, the exceptional uniformity of these polymer-peptide particles makes them amenable to cryo-TEM reconstruction techniques lending insight into their internal structure.
PET for prostate cancer imaging: still a quandary or the ultimate solution? (2002)

Carcinoma of the prostate (PCA) is one of the most common tumors with increasing incidence in elderly men ([1][1]). By the time of diagnosis only 50% of the tumors are clinically localized, and half of these are found to be extracapsular at pathologic staging ([2][2]). Metastases of PCA occur in
A review on the plant microbiome: Ecology, functions, and emerging trends in microbial application (2019)

Plants have evolved with a plethora of microorganisms having important roles for plant growth and health. A considerable amount of information is now available on the structure and dynamics of plant microbiota as well as on the functional capacities of isolated community members. Due to the interesting functional potential of plant microbiota as well as due to current challenges in crop production there is an urgent need to bring microbial innovations into practice. Different approaches for microbiome improvement exist. On the one hand microbial strains or strain combinations can be applied, however, field success is often variable and improvement is urgently required. Smart, knowledge-driven selection of microorganisms is needed as well as the use of suitable delivery approaches and formulations. On the other hand, farming practices or the plant genotype can influence plant microbiota and thus functioning. Therefore, selection of appropriate farming practices and plant breeding leading to improved plant-microbiome interactions are avenues to increase the benefit of plant microbiota. In conclusion, different avenues making use of a new generation of inoculants as well as the application of microbiome-based agro-management practices and improved plant lines could lead to a better use of the plant microbiome. This paper reviews the importance and functionalities of the bacterial plant microbiome and discusses challenges and concepts in regard to the application of plant-associated bacteria.