gebhart/patrepeval huggingface dataset:
DNA methylation and cancer (2000)

The methylation of DNA is an epigenetic modification that can play an important role in the control of gene expression in mammalian cells. The enzyme involved in this process is DNA methyltransferase, which catalyzes the transfer of a methyl group from S-adenosyl-methionine to cytosine residues to form 5-methylcytosine, a modified base that is found mostly at CpG sites in the genome. The presence of methylated CpG islands in the promoter region of genes can suppress their expression. This process may be due to the presence of 5-methylcytosine that apparently interferes with the binding of transcription factors or other DNA-binding proteins to block transcription. In different types of tumors, aberrant or accidental methylation of CpG islands in the promoter region has been observed for many cancer-related genes resulting in the silencing of their expression. How this aberrant hypermethylation takes place is not known. The genes involved include tumor suppressor genes, genes that suppress metastasis and angiogenesis, and genes that repair DNA suggesting that epigenetics plays an important role in tumorigenesis. The potent and specific inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-AZA-CdR) has been demonstrated to reactivate the expression most of these "malignancy" suppressor genes in human tumor cell lines. These genes may be interesting targets for chemotherapy with inhibitors of DNA methylation in patients with cancer and this may help clarify the importance of this epigenetic mechanism in tumorigenesis.
Maternal Infection and Cerebral Palsy in Infants of Normal Birth Weight (1997)

Intrauterine exposure to maternal infection was associated with a marked increase in risk of CP in infants of normal birth weight. Maternal infection was also linked with low Apgar scores, other evidence of hypotension [corrected] and need for resuscitation, and neonatal seizures-signs commonly attributed to birth asphyxia.
Populäre und akademische Literatur zu ‚PC‘ und ‚SC‘ (1999)

Neben dem regen Interesse der Medien an ‚Political Correctness‘ und ‚Sexual Correctness‘ sind in den vergangenen Jahren hierzulande auch einige Monographien zum Thema ‚PC‘ erschienen. Werke zum Thema ‚SC‘ existieren jedoch bislang nicht, und auch wissenschaftliche Aufsätze deutscher Autorinnen und Autoren zu ‚PC‘ bzw. ‚SC‘ sind noch eher rar. Unter den vorhandenen Beiträgen sind zudem viele, die sich hauptsächlich oder sogar ausschließlich mit ‚PC‘ und ‚SC‘ als US-amerikanischen Phänomenen auseinandersetzen.
Influence of the pressure field distribution in transcranial ultrasonic neurostimulation (2013)

Transcranial ultrasonic stimulation is pressure- and anesthesia-dependent in the rat model. Numerical simulations have shown that the acoustic pattern can be complex inside the rat head and that special care must be taken for small animal studies relating acoustic parameters to neurostimulation effects, especially at a low frequency.
Rat Long Chain Acyl-CoA Synthetase 5, but Not 1, 2, 3, or 4, Complements Escherichia coli fadD (2004)

Long chain fatty acids are converted to acyl-CoAs by acyl-CoA synthetase (fatty acid CoA ligase: AMP forming, E.C. 6.2.1.3; ACS). Escherichia coli has a single ACS, FadD, that is essential for growth when fatty acids are the sole carbon and energy source. Rodents have five ACS isoforms that differ in substrate specificity, tissue expression, and subcellular localization and are believed to channel fatty acids toward distinct metabolic pathways. We expressed rat ACS isoforms 1-5 in an E. coli strain that lacked FadD. All rat ACS isoforms were expressed in E. coli fadD or fadDfadR and had ACS specific activities that were 1.6-20-fold higher than the wild type control strain expressing FadD. In the fadD background, the rat ACS isoforms 1, 2, 3, 4 and 5 oxidized [(14)C]oleate at 5 to 25% of the wild type levels, but only ACS5 restored growth on oleate as the sole carbon source. To ensure that enzymes of beta-oxidation were not limiting, assays of ACS activity, beta-oxidation, fatty acid transport, and phospholipid synthesis were also examined in a fadD fadR strain, thereby eliminating FadR repression of the transporter FadL and the enzymes of beta-oxidation. In this strain, fatty acid transport levels were low but detectable for ACS1, 2, 3, and 4 and were nearly 50% of wild type levels for ACS5. Despite increases in beta-oxidation, only ACS5 transformants were able to grow on oleate. These studies show that although ACS isoforms 1-4 variably supported moderate transport activity, beta-oxidation, and phospholipid synthesis and although their in vitro specific activities were greater than that of chromosomally encoded FadD, they were unable to substitute functionally for FadD regarding growth. Thus, membrane composition and protein-protein interactions may be critical in reconstituting bacterial ACS function.
New Role of the Disulfide Stress Effector YjbH in β-Lactam Susceptibility of Staphylococcus aureus (2011)

Staphylococcus aureus is exposed to multiple antimicrobial compounds, including oxidative burst products and antibiotics. The various mechanisms and regulatory pathways governing susceptibility or resistance are complex and only superficially understood. Bacillus subtilis recently has been shown to control disulfide stress responses by the thioredoxin-related YjbH protein, which binds to the transcriptional regulator Spx and controls its degradation via the proteasome-like ClpXP protease. We show that the S. aureus YjbH homolog has a role in susceptibility to the disulfide stress-inducing agent diamide that is similar to that in B. subtilis, and we demonstrate that the four cysteine residues in YjbH are required for this activity. In addition, the inactivation of YjbH led to moderate resistance to oxacillin and other β-lactam antibiotics, and this phenotypic change was associated with higher penicillin-binding protein 4 levels and increased peptidoglycan cross-linking. Of note, the impact of YjbH on β-lactam susceptibility still was observed when the four cysteines of YjbH were mutated, indicating that the roles of YjbH in disulfide stress and β-lactam resistance rely on different types of interactions. These data suggest that the ClpXP adaptor YjbH has more target proteins than previously thought, and that oxidative burst and β-lactam resistance mechanisms of S. aureus are closely linked.
Inverse Relationship Between Cytotoxicity of Free Fatty Acids in Pancreatic Islet Cells and Cellular Triglyceride Accumulation (2001)

Studies in Zucker diabetic fatty rats have led to the concept that chronically elevated free fatty acid (FFA) levels can cause apoptosis of triglyceride-laden pancreatic beta-cells as a result of the formation of ceramides, which induce nitric oxide (NO)-dependent cell death. This "lipotoxicity" hypothesis could explain development of type 2 diabetes in obesity. The present study examines whether prolonged exposure to FFA affects survival of isolated normal rat beta-cells and whether the outcome is related to the occurrence of triglyceride accumulation. A dose-dependent cytotoxicity was detected at 5-100 nmol/l of unbound oleate and palmitate, with necrosis occurring within 48 h and an additional apoptosis during the subsequent 6 days of culture. At equimolar concentrations, the cytotoxicity of palmitate was higher than that of oleate but lower than that of its nonmetabolized analog bromopalmitate. FFA cytotoxicity was not suppressed by etomoxir (an inhibitor of mitochondrial carnitine palmitoyltransferase I) or by antioxidants; it was not associated with inducible NO synthase expression or NO formation. An inverse correlation was observed between the percentage of dead beta-cells on day 8 and their cellular triglyceride content on day 2. For equimolar concentrations of the tested FFA, oleate caused the lowest beta-cell toxicity and the highest cytoplasmic triglyceride accumulation. On the other hand, oleate exerted the highest toxicity in islet non-beta-cells, where no FFA-induced triglyceride accumulation was detected. In conditions without triglyceride accumulation, the lower FFA concentrations caused primarily apoptosis, both in islet beta-cells and non-beta-cells. It is concluded that FFAs can cause death of normal rat islet cells through an NO-independent mechanism. The ability of normal beta-cells to form and accumulate cytoplasmic triglycerides might serve as a cytoprotective mechanism against FFA-induced apoptosis by preventing a cellular rise in toxic free fatty acyl moieties. It is conceivable that this potential is lost or insufficient in cells with a prolonged triglyceride accumulation as may occur in vivo.
Role of the faecal stream in the maintenance of Crohn's colitis. (1985)

The role of the faecal stream in the maintenance of the inflammation in Crohn's disease has been studied. Small bowel effluent and a sterile ultrafiltrate of it were reintroduced into the defunctioned colon of patients with Crohn's colitis treated by split ileostomy. The systemic effect of these challenges on the patients was assessed clinically and by laboratory tests, and the effect on the local disease was assessed by endoscopy, histology, and quantitative analysis of lamina propria plasma cell populations. There was little response to the ultrafiltrate challenge. In contrast the clinical responses to challenge with ileostomy effluent were marked in some patients. One patient relapsed and eight others had clinically detectable responses. On the other hand changes in laboratory, endoscopic, histological, and morphometric tests in response to the faecal challenge were less pronounced. The only significant changes in the laboratory results were a relative lymphopenia (p less than 0.05) and a raised ESR (p less than 0.02) after seven days challenge with the effluent. The plasma cell density also increased but not significantly. In conclusion, these results suggest that factors greater than 0.22 microns in the faecal stream are responsible for the maintenance and exacerbation of inflammation in Crohn's disease.
The effects of cure temperature on the thermomechanical properties of UV curable coatings (1989)

Abstract A method is presented to study the mechanical behavior of soft, UV curable coating material as a function of temperature of the prepolymer at cure. For such materials, the crosslink density (hence, equilibrium modulus) is found to decrease with increasing cure temperature. The three primary coatings are: a polyurethane acrylate with a nominal equilibrium tensile modulus of 200 psi, a polyurethane acrylate with a nominal equilibrium modulus of 1200 psi, and a non‐urethane acrylate with a nominal equilibrium tensile modulus of 60 psi.
Fluorescent, Sequence-Selective Peptide Detection by Synthetic Small Molecules (1998)

Small organic sensor molecules were prepared that bind and signal the presence of unlabeled tripeptides in a sequence-selective manner. Sequence-selective peptide binding is a difficult problem because small peptides are highly flexible and there are no clear rules for designing peptide-binding molecules as there are for the nucleic acids. The signaling system involved the application of fluorescence energy transfer and provided large, real-time fluorescence increases (300 to 500 percent) upon peptide binding. With it, these sensors were sensitive enough to detect unlabeled cognate peptides both in organic solution and in the solid state at low micromolar concentrations.
Diagnostic Imaging of Femoroacetabular Impingement (2013)

Imaging studies play a key role in establishing the diagnosis of femoroacetabular impingement (FAI). When clinical examination is suggestive of FAI, radiographic evidence should confirm the diagnosis. Imaging findings must be evaluated in the context of the patient's clinical presentation and recreational activities. Plain radiographic evaluation remains the initial diagnostic modality. Three-dimensional imaging such as MRI and CT often is obtained for the evaluation of labral and cartilage pathology, definition of bony anatomy, and surgical planning.
Influenza Viruses (2003)

Abstract Influenza viruses are isolated from a variety of animals, including humans and birds. The majority of these viruses cause mild to severe respiratory disease; some produce lethal systemic disease.
Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome (2004)

These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome.
Self-Assembly of Model Collagen Peptide Amphiphiles (2001)

We have used cryo-transmission electron microscopy (cryo-TEM), small-angle neutron scattering (SANS), differential scanning calorimetry (DSC), and circular dichroism (CD) for microstructural characterization of amphiphiles that have a model collagen peptide headgroup. Single-tail amphiphiles and double-tail amphiphiles with short tails such as C12 and C14 formed spheroidal micelles. Further increase in tail length of the double-tail amphiphiles led to the formation of disklike micelles that aggregated to form a strandlike structure. SANS curves for double-tail amphiphiles were obtained at different contrasts by using different fractions of D2O in the D2O/H2O mixture. SANS data analysis using the sphere method confirmed the structures imaged by cryo-TEM and provided a detailed structural characterization. CD data showed that the peptide's capacity to organize into a triple helix by intertwining with two neighboring molecules can be affected by increasing the tail length. Double-tail amphiphiles with tails such as C18 and C20 that are crystalline at room temperature disrupt the association of the triple helix at room temperature. Increasing the temperature to melt the crystalline tails helps restore the triple-helical conformation in the headgroups.
Counterflow centrifugal elutriation: present and future. (1993)

Counterflow centrifugal elutriation (CCE) has been proposed as a method for separating heterogeneous cell populations into distinct subpopulations on the basis of different sedimentation characteristics, without impairment of cell function or yield. The advantages of this technique are the high recovery and viability of fractionated cells and the rapidity and reproducibility of results. CCE alone or in combination with other separation methods can provide homogeneous populations of cells for further investigations. Recently, CCE has been employed in clinical studies aimed at preventing GVHD in BMT recipients by depleting lymphocytes prior to BM infusion. Furthermore, ongoing studies are concentrating on the use of negative selection procedures on the fractions currently excluded from the graft with the purpose of adding these depleted fractions to the graft preparation to augment the number of stem cells, accessory cells and unselected lymphocyte subsets. In the experimental field, CCE combined with negative and positive selection techniques may be useful in the study of hematopoiesis by separating 'pure' stem cell populations from more committed hematopoietic progenitors. We review here the present and possible future applications of elutriation in the clinical and experimental field.
Intelligent Control of Surface Hydrophobicity (2007)

Switchable surfaces are highly useful materials with surface properties that change in response to external stimuli. These surfaces can be employed in both research and industrial applications, where the ability to actively control surface properties can be used to develop smart materials and intelligent surfaces. Herein, we review a range of surfaces in which hydrophobicity can be controlled. We present the principal ideas of surface switching, discuss recent developments, explore experimental issues and examine factors that influence surface switching, including the nature of the stimuli, the underlying material, the morphology of the surface and the surrounding environment. We have categorised switchable surfaces according to the stimuli that trigger changes in surface hydrophobicity. These are electrically, electrochemically, thermally, mechanically, photo- and environmentally inducible surfaces. In addition, we review the use of chemical reactions to modify the properties of switchable surfaces and produce changes in the molecular structure and nanoscale features of the surface.
Control of somatic embryogenesis and embryo development by AP2 transcription factors (2010)

Members of the AP2 family of transcription factors, such as BABY BOOM (BBM), play important roles in cell proliferation and embryogenesis in Arabidopsis thaliana (AtBBM) and Brassica napus (BnBBM) but how this occurs is not understood. We have isolated three AP2 genes (GmBBM1, GmAIL5, GmPLT2) from somatic embryo cultures of soybean, Glycine max (L.) Merr, and discovered GmBBM1 to be homologous to AtBBM and BnBBM. GmAIL5 and GmPLT2 were homologous to Arabidopsis AINTEGUMENTA-like5 (AIL5) and PLETHORA2 (PLT2), respectively. Constitutive expression of GmBBM1 in Arabidopsis induced somatic embryos on vegetative organs and other pleiotropic effects on post-germinative vegetative organ development. Sequence comparisons of BBM orthologues revealed the presence of ten sequence motifs outside of the AP2 DNA-binding domains. One of the motifs, bbm-1, was specific to the BBM-like genes. Deletion and domain swap analyses revealed that bbm-1 was important for somatic embryogenesis and acted cooperatively with at least one other motif, euANT2, in the regulation of somatic embryogenesis and embryo development in transgenic Arabidopsis. The results provide new insights into the mechanisms by which BBM governs embryogenesis.
Targeted Exon Skipping to Address “Leaky” Mutations in the Dystrophin Gene (2012)

Protein-truncating mutations in the dystrophin gene lead to the progressive muscle wasting disorder Duchenne muscular dystrophy, whereas in-frame deletions typically manifest as the milder allelic condition, Becker muscular dystrophy. Antisense oligomer-induced exon skipping can modify dystrophin gene expression so that a disease-associated dystrophin pre-mRNA is processed into a Becker muscular dystrophy-like mature transcript. Despite genomic deletions that may encompass hundreds of kilobases of the gene, some dystrophin mutations appear "leaky", and low levels of high molecular weight, and presumably semi-functional, dystrophin are produced. A likely causative mechanism is endogenous exon skipping, and Duchenne individuals with higher baseline levels of dystrophin may respond more efficiently to the administration of splice-switching antisense oligomers. We optimized excision of exons 8 and 9 in normal human myoblasts, and evaluated several oligomers in cells from eight Duchenne muscular dystrophy patients with deletions in a known "leaky" region of the dystrophin gene. Inter-patient variation in response to antisense oligomer induced skipping in vitro appeared minimal. We describe oligomers targeting exon 8, that unequivocally increase dystrophin above baseline in vitro, and propose that patients with leaky mutations are ideally suited for participation in antisense oligomer mediated splice-switching clinical studies.Molecular Therapy - Nucleic Acids (2012) 1, e48; doi:10.1038/mtna.2012.40; published online 16 October 2012.
Intramolecular Hydrogen Bonding in Medicinal Chemistry (2010)

The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we derive propensities for intramolecular hydrogen bond formation of five- to eight-membered ring systems of relevance in drug discovery. A number of motifs, several of which are clearly underutilized in drug discovery, are analyzed in more detail by comparing small molecule and protein-ligand X-ray structures. To investigate effects on physicochemical properties, sets of closely related structures with and without the ability to form intramolecular hydrogen bonds were designed, synthesized, and characterized with respect to membrane permeability, water solubility, and lipophilicity. We find that changes in these properties depend on a subtle balance between the strength of the hydrogen bond interaction, geometry of the newly formed ring system, and the relative energies of the open and closed conformations in polar and unpolar environments. A number of general guidelines for medicinal chemists emerge from this study.
Identification of Bone Marrow-Derived Soluble Factors Regulating Human Mesenchymal Stem Cells for Bone Regeneration (2017)

Maintaining properties of human bone marrow-derived mesenchymal stem cells (BMSCs) in culture for regenerative applications remains a great challenge. An emerging approach of constructing a culture environment mimicking the bone marrow niche to regulate BMSC activities has been developed. In this study, we have demonstrated a systematic approach to identify soluble factors of interest extracted from human bone marrow and used them in BMSC culture for tissue regeneration. We have found that lipocalin-2 and prolactin are key factors in bone marrow, involved in regulating BMSC activities. Treating the cell with lipocalin-2 and prolactin delays cellular senescence of BMSCs and primes the cell for osteogenesis and chondrogenesis. We have also demonstrated that BMSCs pretreated with lipocalin-2 and prolactin can enhance the repair of calvarial defects in mice. Together, our study provides research evidence of using a viable approach to prime BMSC properties in vitro for improving cell-based tissue regeneration in vivo.
Split-Row: A Reduced Complexity, High Throughput LDPC Decoder Architecture (2006)

A reduced complexity LDPC decoding method is presented that dramatically reduces wire interconnect complexity, which is a major issue in LDPC decoders. The proposed split-row method makes column processing parallelism easier to exploit, doubles available row processor parallelism, and significantly simplifies row processors - which results in smaller area, higher speeds, and lower energy dissipation. Simulation results over an additive white Gaussian channel show that the error performance of high row-weight codes with split-row decoding is within 0.3-0.6 dB of the min-sum and sum-product decoding algorithms. A full parallel decoder for a (3,6) LDPC code with a code length of 1536 bits is implemented in a 0.18 mum CMOS technology twice: once using the split-row method, and once using the min-sum algorithm for comparison. The split-row decoder operates at 53 MHz and delivers a throughput of 5.4 Gbps with 15 decoding iterations per block. The split-row decoder is about 1.3 times smaller, has an average wire length 1.5 times shorter, and has a throughput 1.6 times higher than the min-sum decoder.