gebhart/patrepeval huggingface dataset:
Disruption of Higher-Order Folding by Core Histone Acetylation Dramatically Enhances Transcription of Nucleosomal Arrays by RNA Polymerase III (1998)

We have examined the effects of core histone acetylation on the transcriptional activity and higher-order folding of defined 12-mer nucleosomal arrays. Purified HeLa core histone octamers containing an average of 2, 6, or 12 acetates per octamer (8, 23, or 46% maximal site occupancy, respectively) were assembled onto a DNA template consisting of 12 tandem repeats of a 208-bp Lytechinus 5S rRNA gene fragment. Reconstituted nucleosomal arrays were transcribed in a Xenopus oocyte nuclear extract and analyzed by analytical hydrodynamic and electrophoretic approaches to determine the extent of array compaction. Results indicated that in buffer containing 5 mM free Mg2+ and 50 mM KCl, high levels of acetylation (12 acetates/octamer) completely inhibited higher-order folding and concurrently led to a 15-fold enhancement of transcription by RNA polymerase III. The molecular mechanisms underlying the acetylation effects on chromatin condensation were investigated by analyzing the ability of differentially acetylated nucleosomal arrays to fold and oligomerize. In MgCl2-containing buffer the folding of 12-mer nucleosomal arrays containing an average of two or six acetates per histone octamer was indistinguishable, while a level of 12 acetates per octamer completely disrupted the ability of nucleosomal arrays to form higher-order folded structures at all ionic conditions tested. In contrast, there was a linear relationship between the extent of histone octamer acetylation and the extent of disruption of Mg2+-dependent oligomerization. These results have yielded new insight into the molecular basis of acetylation effects on both transcription and higher-order compaction of nucleosomal arrays.
Tamoxifen-induced increase in the potential doubling time of MCF-7 xenografts as determined by bromodeoxyuridine labeling and flow cytometry. (1993)

The anti-estrogen tamoxifen (TAM) is widely used in the therapy of human breast cancer. Shown to induce a G1 transition delay in vitro, the kinetic effects of TAM on breast carcinoma cells growing as tumor xenografts in nude mice have been less well characterized. In this study, we demonstrate a significant increase in the tumor potential doubling time (Tpot) and decrease in the labeling index (%LI) of estradiol (E2)-stimulated MCF-7 xenografts following TAM treatment or E2 deprivation. MCF-7 tumor pieces were transplanted s.c. into nude mice supplemented with Silastic capsules containing E2. After 2-4 weeks, animals were randomized to continued E2 treatment, E2 and TAM treatment, or E2 deprivation. At times ranging from 0 to 23 days after treatment, animals were given injections of bromodeoxyuridine and tumors excised for kinetic analysis. Using flow-cytometric techniques, the Tpot and %LI were estimated for all tumors. Seven independent experiments were performed and data pooled for statistical analysis. At the time of hormonal manipulation, E2-stimulated tumors had a volume doubling time of 5 days, a Tpot of 2.3 days, and a %LI of 23%. Continued E2 treatment resulted in only minimal changes in Tpot and %LI over the remainder of the observation period. Treatment with TAM resulted in a slowing of tumor growth (tumor doubling time, 12 days), a significant (P < 0.001) increase in Tpot to 6.6 days, and a decrease in %LI to 8% by 23 days posttreatment. E2 deprivation resulted in a cessation of tumor growth and similar changes in Tpot and %LI to 5.3 days and 10%, respectively (P < 0.001). In contrast to previous reports, these data demonstrate that TAM treatment and E2 deprivation both significantly decrease tumor cell proliferation in MCF-7 xenografts.
Infrared Study of the OH Groups in Expanded Kaolinite (1964)

Expansion of kaolinite with potassium acetate and with hydrazine followed by deuteration, shifts the absorption frequency at 3695 cm(-1) to lower values, but does not aflect the intensity of the 3620-cm(-1) absorption band. The band at 3695 cm(-1) is correlated predominantly to inner-surface hydroxyls with the dipole at right angles to the basal plane and the band at 3620 cm(-1) is related to inner hydroxyls with the dipole inclined toward empty octahedral sites.
Cytokine phenotype of human autoreactive T cell clones specific for the immunodominant myelin basic protein peptide (83–99) (1996)

Experimental allergic encephalomyelitis (EAE), an animal model resembling multiple sclerosis (MS), is mediated by myelin antigen-specific CD4+ T cells secreting cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-β (TNF-β), and the proinflammatory cytokine TNF-α—all associated with the T-helper-1 (Th1) T cell subset. Based on numerous similarities between MS and EAE, it has been postulated that Th1-like T cells are involved in the pathogenesis of MS. Production of proinflammatory cytokines such as IFN-γ and, in particular, TNF-α/β by autoreactive T cells is considered crucial for the initiation and amplification of inflammatory brain lesions and possibly also for direct myelin damage. In contrast, regulatory cytokines such as interleukin-4 (IL-4), IL-10, and IL-13, which are associated with the Th2-like phenotype, may play a role in the resolution of relapses. Although the human T cell response to myelin basic protein (MBP) is well characterized in terms of antigen specificity, HLA restriction, and T cell-receptor (TCR) usage, little is known about the cytokine pattern of these autoreactive T cells. To gain such information, conditions for studying cytokine secretion by human autoreactive T cell clones (TCC) were established. The cytokine secretion profile of human autoreactive CD4+ TCC, specific for myelin basic protein peptide (83–89) [MBP(83–99)], a candidate autoantigen in MS, was investigated. Our results show that TCC cytokine production in long-term culture was stable. In addition, the correlation of various cytokines within specific TCC revealed differences compared to murine T cells. The comparison of 30 human MBP(83–99)-specific TCC demonstrated heterogeneity in cytokine secretion, with a continuum between Th1- and Th2-like cells rather than distinct Th1 or Th2 subsets. These data are important for further investigation of the potential role of cytokines in the inflammatory process of MS, and provide a powerful tool to investigate therapeutic interventions with respect to their influence on cytokine secretion of autoreactive T cells. © 1996 Wiley-Liss, Inc.
Identification of a cell‐surface glycoprotein mediating cell adhesion in EBV‐immortalized normal B cells (1986)

Phorbol ester treatment markedly enhanced aggregation of Epstein-Barr virus (EBV)-immortalized normal B cells. Monoclonal antibody (MAb) 60.3, recognizing a leukocyte common antigen, completely inhibited intracellular adhesion, whereas MAbs reacting with leukocyte common antigen T200, C3b receptor, T-cell-associated antigen TA-I, C3d (EBV) receptor, brain-granulocyte/T-lymphocyte antigen, transferrin receptor, surface immunoglobulin, Class-I or Class-II transplantation antigens or a B-cell-specific antigen (BI) showed no inhibitory effect. Both the spontaneous and phorbol-ester-enhanced cell aggregations were similarly inhibited by Fab fragments made from antibody 60.3. Phorbol esters also enhance binding between EBV-immortalized normal B cells and autologous or allogeneic blood mononuclear cells depleted of B lymphocytes. This process, which is independent of immunity to EBV, was similarly blocked by the antibody fragments. Antibody 60.3 precipitated 3 non-covalently associated surface glycopolypeptides with apparent MW of 90, 130 and 160/kDa from EBV-infected B cells. Although dissociation of a similar protein complex from granulocytes by sodium dodecyl sulfate treatment clearly indicated the presence of the epitope on the smallest component, the same treatment did not dissociate the protein complex from EBV-immortalized normal B cells. It is thus concluded that the 90-kDa glycopolypeptide, either alone or associated with the larger glycopolypeptides, mediates cell adhesion of the B cells.
THE EFFECT OF RECOMBINANT BASIC FIBROBLAST GROWTH FACTOR (bFGF) IN FIBRIN ADHESIVE VEHICLE ON THE HEALING OF ISCHAEMIC AND NORMAL INCISIONAL SKIN WOUNDS (1998)

Normal and ischaemic incisional wounds in rats were treated with recombinant human basic fibroblast growth factor (rbFGF) in fibrin adhesive vehicle. After 10 days of healing the maximum load*S and stress*S (S denotes correction for shrinkage) of ischaemic wounds were increased by 45% and 39%, respectively, after treatment with 20 micrograms rbFGF and by 67% and 56% after treatment with 60 micrograms rbFGF. After 20 days only 20 micrograms rbFGF had any effect and increased maximum load*S by 31% and energy at maximum (load*S, stress*S) by 40%-48%. In normal wounds 0.6-20 micrograms and 60 micrograms rbFGF decreased the strength parameters by 19%-34% and 49%-52%, respectively, after 10 days. After 20 days there was no negative influence but 60 micrograms rbFGF increased the biomechanical properties by 15%-24%. Treatment with the fibrin adhesive vehicle alone decreased the biomechanical properties of ischaemic wounds after 20 days, and of normal wounds after both 10 and 20 days. In conclusion, rbFGF can improve the healing of ischaemic wounds and may be used in the treatment of ischaemic wounds in patients, but it can have negative effects on normal wound healing.
Lattice-Based Memory Allocation (2003)

Abstract—We investigate the problem of memory reuse in order to reduce the memory needed to store an array variable. We develop techniques that can lead to smaller memory requirements in the synthesis of dedicated processors or to more effective use by compiled code of software-controlled scratchpad memory. Memory reuse is well-understood for allocating registers to hold scalar variables. Its extension to arrays has been studied recently for multimedia applications, for loop parallelization, and for circuit synthesis from recurrence equations. In all such studies, the introduction of modulo operations to an otherwise affine mapping (of loop or array indices to memory locations) achieves the desired reuse. We develop here a new mathematical framework, based on critical lattices, that subsumes the previous approaches and provides new insight. We first consider the set of indices that conflict, those that cannot be mapped to the same memory cell. Next, we construct the set of differences of conflicting indices. We establish a correspondence between a valid modular mapping and a strictly admissible integer lattice—one having no nonzero element in common with the set of conflicting index differences. The memory required by an optimal modular mapping is equal to the determinant of the corresponding lattice. The memory reuse problem is thus reduced to the (still interesting and nontrivial) problem of finding a strictly admissible integer lattice of least determinant. We then propose and analyze several practical strategies for finding strictly admissible integer lattices, either optimal or optimal up to a multiplicative factor, and, hence, memory-saving modular mappings. We explain and analyze previous approaches in terms of our new framework. Index Terms—Program transformation, memory size reduction, admissible lattice, successive minima. 1
Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers (2014)

Transcription factors control the fate of a cell by regulating the expression of genes and regulatory networks. Recent successes in inducing pluripotency in terminally differentiated cells as well as directing differentiation with natural transcription factors has lent credence to the efforts that aim to direct cell fate with rationally designed transcription factors. Because DNA-binding factors are modular in design, they can be engineered to target specific genomic sequences and perform pre-programmed regulatory functions upon binding. Such precision-tailored factors can serve as molecular tools to reprogramme or differentiate cells in a targeted manner. Using different types of engineered DNA binders, both regulatory transcriptional controls of gene networks, as well as permanent alteration of genomic content, can be implemented to study cell fate decisions. In the present review, we describe the current state of the art in artificial transcription factor design and the exciting prospect of employing artificial DNA-binding factors to manipulate the transcriptional networks as well as epigenetic landscapes that govern cell fate.
The maximal affinity of ligands (1999)

We explore the question of what are the best ligands for macromolecular targets. A survey of experimental data on a large number of the strongest-binding ligands indicates that the free energy of binding increases with the number of nonhydrogen atoms with an initial slope of approximately -1.5 kcal/mol (1 cal = 4.18 J) per atom. For ligands that contain more than 15 nonhydrogen atoms, the free energy of binding increases very little with relative molecular mass. This nonlinearity is largely ascribed to nonthermodynamic factors. An analysis of the dominant interactions suggests that van der Waals interactions and hydrophobic effects provide a reasonable basis for understanding binding affinities across the entire set of ligands. Interesting outliers that bind unusually strongly on a per atom basis include metal ions, covalently attached ligands, and a few well known complexes such as biotin-avidin.
Loading effect in SiGe layers grown by dichlorosilane- and silane-based epitaxy (2001)

The evolution of the loading effect in Si1−xGex layers (0⩽x⩽20%) versus growth parameters has been investigated for selective and nonselective growth using silane- and dichlorosilane-based epitaxy. Various methods have been examined in order to reduce the loading effect, and their influence on the defect density will be further discussed. High-resolution x-ray diffraction and atomic force microscopy were applied as the main tools in these investigations. It is shown that SiGe epitaxy is strongly sensitive to the opening size on the patterned substrates. This dependence is affected by the chemistry of the deposition. This effect can be decreased by adding HCl to the gas mixture or decreasing the growth rate. Meanwhile, adding HCl during the growth of SiGe layers or using a low growth rate decreases the epitaxial quality of the layers. Depositing a Si seed layer prior to the growth of the SiGe layer reduces the loading effect without degrading the epitaxial quality of the layer.
A self-routing WDM high-capacity SONET ring network (1992)

A dynamic control mechanism, based on subcarrier-multiplexed pilot-tones and acoustooptic tunable filters, is proposed for wavelength routing in a high-capacity wavelength division multiplexed (WDM) SONET interoffice ring network. The authors experimentally verified the network concept and discussed different network applications for bursty data traffic and continuous voice/video traffic.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Replacement of Histidine 340 with Alanine Inactivates the Group A Streptococcus Extracellular Cysteine Protease Virulence Factor (2000)

Streptococcus pyogenes expresses a highly conserved extracellular cysteine protease that is a virulence factor for invasive disease, including soft tissue infection. Site-directed mutagenesis was used to generate a His340Ala recombinant mutant protein that was made as a stable 40-kDa zymogen by Escherichia coli. Purified His340Ala protein was proteolytically inactive when bovine casein and human fibronectin were used as substrates. Wild-type 28-kDa streptococcal protease purified from S. pyogenes processed the 40-kDa mutant zymogen to a 28-kDa mature form, a result suggesting that the derivative protein retained structural integrity. The data are consistent with the hypothesis that His340 is an enzyme active site residue, an idea confirmed by recent solution of the zymogen crystal structure (T. F. Kagawa, J. C. Cooney, H. M. Baker, S. McSweeney, M. Liu, S. Gubba, J. M. Musser, and E. N. Baker, Proc. Natl. Acad. Sci. USA 97:2235-2240, 2000). The data provide additional insight into structure-function relationships in this S. pyogenes virulence factor.
Binding of the basement-membrane glycoprotein laminin to glycosaminoglycans. An affinity-chromatography study (1981)

The binding of the basement-membrane glycoprotein laminin to glycosaminoglycans (aggregating and non-aggregating subsets of heparan sulphates and dermatan sulphates, as well as heparin, chondroitin sulphates and hyaluronic acid) was studied by affinity chromatography. Partially periodate-oxidized chains of glycosaminoglycans were coupled to adipic acid dihydrazide-substituted agarose. Co-polymeric glycosaminoglycans reveal high affinity for laminin, whereas hyaluronic acid does not. Competitive-release experiments indicate that glycosaminoglycans share a common binding site on the laminin molecule.
Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes (2011)

A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.
Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. (1995)

Dendritic cells (DC) in nonlymphoid organs can internalize and process foreign antigens before migrating to secondary lymphoid tissues to initiate primary immune responses. However, there is little information on which stimuli promote migration of DC from the tissues. Systemic administration of lipopolysaccharide (LPS), which induces in vivo production of cytokines, led to a reduction in the numbers of major histocompatibility complex class II-positive (Ia+) leukocytes in mouse hearts and kidneys: > 95% of DC were depleted 1-3 d after injection of 50 micrograms LPS. Several lines of evidence indicated that this response was due to migration of DC rather than loss of Ia expression or cytotoxic effects. In skin of treated mice, the number of Ia+ epidermal Langerhans' cells (LC) was reduced, and "cords" of Ia+ leukocytes became evident in the dermis. The latter cells expressed little NLDC145 and may have originated from recruited or resident DC progenitors. Systemic administration of recombinant tumor necrosis factor (rhTNF)-alpha resulted in a decrease in numbers of Ia+ cells in heart and kidney and of epidermal LC, and it also induced dermal cords. Administration of a rh-interleukin (IL)-1 resulted in a decrease in Ia+ cells only in renal medulla, appeared to activate a subset of epidermal LC, and induced dermal cords. Similar microgram doses of rhIL-2 had no obvious effect. Treatment with a neutralizing anti-TNF antiserum before LPS administration inhibited the depletion of LC from skin but not from heart or kidney. Therefore, TNF-alpha and IL-1 alpha may promote DC migration from nonlymphoid tissues and may have differential effects on different DC populations, but it is unclear whether they act on DC directly or indirectly (e.g., via other cytokines).
Fractalkine Signaling Regulates the Inflammatory Response in an α-Synuclein Model of Parkinson Disease (2015)

Our results suggest that one mechanism by which CX3CR1-/- attenuates inflammation is at the level of phagocytosis of aggregated α-syn by microglia. These data implicate fractalkine signaling as a potential therapeutic target for regulating inflammatory response in α-syn models PD.
Pharmacological modulation of GITRL/GITR system: therapeutic perspectives (2011)

Glucocorticoid-induced TNFR-related (gitr) is a gene coding for a member of the TNF receptor superfamily. GITR activation by its ligand (GITRL) influences the activity of effector and regulatory T cells, thus participating in the development of immune response against tumours and infectious agents, as well as in autoimmune and inflammatory diseases. Notably, treating animals with GITR-Fc fusion protein ameliorates autoimmune/inflammatory diseases while GITR triggering, by treatment with anti-GITR mAb, is effective in treating viral, bacterial and parasitic infections, as well in boosting immune response against tumours. GITR modulation has been indicated as one of the top 25 most promising research areas by the American National Cancer Institute, and a clinical trial testing the efficacy of an anti-GITR mAb in melanoma patients has been started. In this review, we summarize results regarding: (i) the mechanisms by which GITRL/GITR system modulates immune response; (ii) the structural and functional studies clearly demonstrating differences between GITRL/GITR systems of mice and humans; (iii) the molecules with pharmacological activities including anti-GITR mAbs, GITR-Fc and GITRL-Fc fusion proteins, GITRL in monomer or multimer conformation; and (iv) the possible risks deriving from GITRL/GITR system pharmacological modulation. In conclusion, GITR triggering and inhibition could be useful in treating tumours, infectious diseases, as well as autoimmune and inflammatory diseases. However, differences between mouse and human GITRL/GITR systems suggest that further preclinical studies are needed to better understand how safe therapeutic results can be obtained and to design appropriate clinical trials.
THE SYSTEM ETHANOL-METHANOL AT 40 °C. (1942)

The system ethanol-methanol was studied at 40 °C. using the original and also a modified form of the apparatus of Ferguson and Funnell. The total pressure curve is linear and the partial pressure curves agree with Raoult's law within the experimental error.
Activation of the NOTCH1 pathway in chronic lymphocytic leukemia (2012)

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and is characterized by the monoclonal expansion of CD5+ B cells. CLL shows clinical heterogeneity, from patients with very stable disease to patients with a rapidly progressive disease that is refractory to therapy. In
Measurement of the consistency of patellar-tendon-bearing cast rectification (2003)

The quality of fit of a trans-tibial patellar-tendon-bearing (PTB) socket may be influenced by consistency in casting, rectification or alignment. This paper quantifies, for the first time, the variations in the rectified casts between two experienced prosthetists and the variation between the rectified casts of each individual prosthetist. Prosthetists A and B observed the hand casting of a typical trans-tibial amputee. Each prosthetist was supplied with 5 previously measured duplicated plaster models. The two prosthetists rectified the supplied plaster models based on their own interpretation of basic rectification guidelines. Both prosthetists operated in isolation. The re-measured rectified plaster model data was compared with the unrectified data. The extent of rectification at each of 1800 locations per plaster model was calculated. In zones of major rectification, the mean difference between prosthetists was quantified as 2mm and the standard deviation (SD) about that mean was +/- 1mm for each prosthetist. The co-ordinates of the apex of the fibular head for the 10 modified casts indicated that the maximum variation was in the axial direction with a SD of 4.3mm for prosthetist A and a SD of 2.8mm for prosthetist B. The lengths of the 5 plaster models rectified by prosthetist A indicated a SD of 0.2mm whereas the lengths of the 5 plaster models rectified by prosthetist B indicated a SD of 2.9mm.