gebhart/patrepeval huggingface dataset:
The Drosophila melanogaster Translational Repressor Pumilio Regulates Neuronal Excitability (2002)

Maintenance of proper neuronal excitability is vital to nervous system function and normal behavior. A subset of Drosophila mutants that exhibit altered behavior also exhibit defective motor neuron excitability, which can be monitored with electrophysiological methods. One such mutant is the P-element insertion mutant bemused (bem). The bem mutant exhibits female sterility, sluggishness, and increased motor neuron excitability. The bem P element is located in the large intron of the previously characterized translational repressor gene pumilio (pum). Here, by several criteria, we show that bem is a new allele of pum. First, ovary-specific expression of pum partially rescues bem female sterility. Second, pum null mutations fail to complement bem female sterility, behavioral defects, and neuronal hyperexcitability. Third, heads from bem mutant flies exhibit greatly reduced levels of Pum protein and the absence of two pum transcripts. Fourth, two previously identified pum mutants exhibit neuronal hyperexcitability. Fifth, overexpression of pum in the nervous system reduces neuronal excitability, which is the opposite phenotype to pum loss of function. Collectively, these findings describe a new role of pum in the regulation of neuronal excitability and may afford the opportunity to study the role of translational regulation in the maintenance of proper neuronal excitability.
Cellular Mechanisms Underlying Complete Hematological Response of Chronic Myeloid Leukemia to BRAF and MEK1/2 Inhibition in a Patient with Concomitant Metastatic Melanoma (2015)

These studies suggest that further evaluation of the optimal MAPK targeting approach is warranted to extend therapeutic options in CML.
Not all SCN1A epileptic encephalopathies are Dravet syndrome (2017)

Here, we present a phenotype-genotype correlation for <i>SCN1A</i>. We describe a distinct <i>SCN1A</i> phenotype, early infantile <i>SCN1A</i> encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met.
Nuclear domains of the RNA subunit of RNase P (1997)

The ribonucleoprotein enzyme RNase P catalyzes the 5' processing of pre-transfer RNA, and has also recently been implicated in pre-ribosomal RNA processing. In the present investigation, in situ hybridization revealed that RNase P RNA is present throughout the nucleus of mammalian cells. However, rhodamine-labeled human RNase P RNA microinjected into the nucleus of rat kidney (NRK) epithelial cells or human (HeLa) cells initially localized in nucleoli, and subsequently became more evenly distributed throughout the nucleus, similar to the steadystate distribution of endogenous RNase P RNA. Parallel microinjection and immunocytochemical experiments revealed that initially nucleus-microinjected RNase P RNA localized specifically in the dense fibrillar component of the nucleolus, the site of pre-rRNA processing. A mutant RNase P RNA lacking the To antigen binding domain (nucleotides 25-75) did not localize in nucleoli after nuclear microinjection. In contrast, a truncated RNase P RNA containing the To binding domain but lacking nucleotides 89-341 became rapidly localized in nucleoli following nuclear microinjection. However, unlike the full-length RNase P RNA, this 3' truncated RNA remained stably associated with the nucleoli and did not translocate to the nucleoplasm. These results suggest a nucleolar phase in the maturation, ribonucleoprotein assembly or function of RNase P RNA, mediated at least in part by the nucleolar To antigen. These and other recent findings raise the intriguing possibility of a bifunctional role of RNase P in the nucleus: catalyzing pre-ribosomal RNA processing in the nucleolus and pre-transfer RNA processing in the nucleoplasm.
Identification of an additional member of the protein-tyrosine-phosphatase family: evidence for alternative splicing in the tyrosine phosphatase domain. (1990)

Protein-tyrosine-phosphatases (protein-tyrosine-phosphate phosphohydrolase, EC 3.13.48) have been implicated in the regulation of cell growth; however, to date few tyrosine phosphatases have been characterized. To identify additional family members, the cDNA for the human tyrosine phosphatase leukocyte common antigen (LCA; CD45) was used to screen, under low stringency, a mouse pre-B-cell cDNA library. Two cDNA clones were isolated and sequence analysis predicts a protein sequence of 793 amino acids. We have named the molecule LRP (LCA-related phosphatase). RNA transfer analysis indicates that the cDNAs were derived from a 3.2-kilobase mRNA. The LRP mRNA is transcribed in a wide variety of tissues. The predicted protein structure can be divided into the following structural features: a short 19-amino acid leader sequence, an exterior domain of 123 amino acids that is predicted to be highly glycosylated, a 24-amino acid membrane-spanning region, and a 627-amino acid cytoplasmic region. The cytoplasmic region contains two approximately 260-amino acid domains, each with homology to the tyrosine phosphatase family. One of the cDNA clones differed in that it had a 108-base-pair insertion that, while preserving the reading frame, would disrupt the first protein-tyrosine-phosphatase domain. Analysis of genomic DNA indicates that the insertion is due to an alternatively spliced exon. LRP appears to be evolutionarily conserved as a putative homologue has been identified in the invertebrate Styela plicata.
A Pan‐Specific Inhibitor of the Polo‐Box Domains of Polo‐like Kinases Arrests Cancer Cells in Mitosis (2009)

Playing polo: Small-molecule inhibitors of polo-like kinase 1 are mostly ATP-competitive, and thus face enormous specificity hurdles. This communication explores the concept of inhibiting Plk1 with a small-molecule inhibitor of the protein-protein interactions required for Plk1 function.
Cerebral ischemia and inflammation (2001)

Cerebral ischemia is accompanied by a marked inflammatory reaction that is initiated by ischemia-induced expression of cytokines, adhesion molecules, and other inflammatory mediators, including prostanoids and nitric oxide. Preclinical studies suggest that interventions that are aimed at attenuating such inflammation reduce the progression of brain damage that occurs during the late stages of cerebral ischemia. In particular, strategies that block the activity of inflammation-related enzymes, such as inducible nitric oxide synthase and cyclo-oxygenase-2, reduce ischemic damage with an extended therapeutic window. Although a clinical trial using murine antibodies against intercellular adhesion molecule-1 did not show benefit in patients with ischemic stroke, recent data indicate that immune activation induced by the heterologous protein may have played an important role in the failure of this trial. Therefore, there is a strong rationale for continuing to explore the efficacy of anti-inflammatory therapies in the treatment of the late stages of cerebral ischemia.
Magnetic resonance imaging of perfusion (1990)

Recent developments have shown that diffusion and blood microcirculation (perfusion) could be imaged and measured noninvasively by MRI. The purpose of this presentation is to overview the different approaches that use B0 field gradients to monitor diffusion/perfusion. The principles of these different methods are discussed together with their limitations and their potential applications.
T Cell Subsets and the Recognition of MHC Class (1983)

We have presented and/or briefly reviewed data which indicates that there are two T cell subsets which interact respectively with the two Classes (1 and 2) of MHC antigen and which can be identified by the Ly (mouse) or Leu (human) molecules that they express. This correlation, and the large body of (largely) circumstantial but still quite convincing data, suggests that these Ly and Leu molecules play a very important role in T cell responses by actually interacting with monomorphic MHC class specific determinants. We suggest that this interaction facilitates and possibly helps direct the binding of the T cell receptor to polymorphic MHC determinants and antigen. In this model T cell "recognition" of MHC and antigen consists of several independent but connected interactions of T cell surface structure with MHC molecules and antigen on antigen-presenting cells or targets.
THE DEVELOPMENTAL POTENTIALITY OF THE LIVER-RNA-TREATED POSTERIOR PRIMITIVE STREAK IN THE CHICK EMBRYO (1968)

The posterior third of the primitive streak was implanted into the 2 ½-day chick embryo. Both growth and differentiation of the untreated implants were similar to those of the serum albumin series. Treatment with liver RNA, however, resulted in a significant increase in the rate of growth and differentiation. When liver RNA was incubated with RNase, the products furthered the growth and feather bud formation, but reduced the differentiation of the endodermal derivatives, especially gut.
The Logic of Automated Glycan Assembly (2015)

Carbohydrates are the most abundant biopolymers on earth and part of every living creature. Glycans are essential as materials for nutrition and for information transfer in biological processes. To date, in few cases a detailed correlation between glycan structure and glycan function has been established. A molecular understanding of glycan function will require pure glycans for biological, immunological, and structural studies. Given the immense structural complexity of glycans found in living organisms and the lack of amplification methods or expression systems, chemical synthesis is the only means to access usable quantities of pure glycan molecules. While the solid-phase synthesis of DNA and peptides has become routine for decades, access to glycans has been technically difficult, time-consuming and confined to a few expert laboratories. In this Account, the development of a comprehensive approach to the automated synthesis of all classes of mammalian glycans, including glycosaminoglycans and glycosylphosphatidyl inositol (GPI) anchors, as well as bacterial and plant carbohydrates is described. A conceptual advance concerning the logic of glycan assembly was required in order to enable automated execution of the synthetic process. Based on the central glycosidic bond forming reaction, a general concept for the protecting groups and leaving groups has been developed. Building blocks that can be procured on large scale, are stable for prolonged periods of time, but upon activation result in high yields and selectivities were identified. A coupling-capping and deprotection cycle was invented that can be executed by an automated synthesis instrument. Straightforward postsynthetic protocols for cleavage from the solid support as well as purification of conjugation-ready oligosaccharides have been established. Introduction of methods to install selectively a wide variety of glycosidic linkages has enabled the rapid assembly of linear and branched oligo- and polysaccharides as large as 30-mers. Fast, reliable access to defined glycans that are ready for conjugation has given rise to glycan arrays, glycan probes, and synthetic glycoconjugate vaccines. While an ever increasing variety of glycans are accessible by automated synthesis, further methodological advances in carbohydrate chemistry are needed to make all possible glycans found in nature. These tools begin to fundamentally impact the medical but also materials aspects of the glycosciences.
A Novel Minimized Computational Time Based Encryption and Authentication Using ECDSA (2013)

Providing the security on the basis of encryption standards is considered as key challenges for achieving the integrity & confidentiality. There are three main public-key cryptosystem contenders. Each has a variable key size that can be increased to achieve higher security at the cost of slower cryptographic operations. The best attack known on each public-key cryptosystem requires an amount of computation determined by a security parameter which is related to the key size. The secondary factor is confidentiality i.e. ensuring that adversaries gain no intelligence from a transmitted message. There are two major techniques for achieving confidentiality:
Developing and maintaining protective CD8+ memory T cells (2006)

A critical aim of vaccine-related research is to identify the mechanisms by which memory T cells are formed and maintained over long periods of time. In recent years, we have designed experiments aimed at addressing two key questions: (i) what are the factors that maintain functionally responsive CD8+ memory cells over long periods of time, and (ii) what are the signals during the early stages of infection that drive the differentiation of long-lived CD8+ memory T cells? We have identified a role for CD4+ T cells in the generation of CD8+ T-cell-mediated protection from secondary challenge. While CD4+ T cells appear to play a role in the programme of CD8 memory, we find that they are also required for the long-term maintenance of CD8+ memory T-cell numbers and function. This property is independent of CD40-CD40L interactions, and we propose a role for CD4+ T cells in maintaining the ability of CD8+ memory T cells to respond to interleukin-7 (IL-7) and IL-15. By manipulating both the time course of infection and the timing of antigen presentation to newly recruited CD8+ T cells, we also demonstrate that the programming of effector and memory potential are at least partially distinct processes.
Biosynthesis and assembly of alcohol oxidase, a peroxisomal matrix protein in methylotrophic yeasts: A review (1991)

Alcohol oxidase (AO) catalyses the first step of methanol metabolism in yeasts. In vivo the enzyme is compartmentalized in special cell compartments, called peroxisomes. The enzyme along with the organelles are induced during growth of methylotrophic yeasts on methanol as the sole carbon source. Like all other peroxisomal matrix proteins, AO is encoded by a nuclear gene. Expression of the protein is regulated by a repression/derepression mechanism, but also by induction. Inactive monomeric precursor protein is synthesized in the cytosol and subsequently imported post-translationally into peroxisomes without further processing. Assembly into the active homo-octameric enzyme and binding of the prosthetic group flavin adenine dinucleotide occurs inside the organelle. When enhanced concentration of octameric alcohol oxidase are present in the organelles, the enzyme may form a crystalloid. Oligomerization is not dependent on translocation of AO precursors into their target organelle since octameric, active AO is detected in the cytosol and nucleus of peroxisome-deficient mutants of Hansenula polymorpha: at high expression rates large cytosolic AO crystalloids are formed, which occasionally are also encountered inside the nucleus of such mutants. This paper summarizes recent findings and views on the mechanisms involved in synthesis, import, assembly and crystallization of this important peroxisomal enzyme.
Atherosclerotic plaque composition among patients with stenotic coronary artery disease on noninvasive CT angiography (2010)

Significant differences in plaque composition according to severity of CAD were observed in our study. Individuals with a higher likelihood of stenotic CAD were more likely to have higher underlying burden of exclusively calcified and mixed plaque. These findings should stimulate further investigations to assess the prognostic value of plaque according to their underlying composition.
The neurobiology of stress and gastrointestinal disease (2000)

The role of stress in the modulation of the most common gastrointestinal disorders has traditionally been considered a domain of psychology, and has frequently been lumped together with the role of psychiatric comorbidity. Among clinicians, the term “stress” is generally taken as synonymous with psychological (“exteroceptive”) stress. Based on the deeply ingrained Cartesian view in medicine and gastroenterology, stress and psychological factors have been considered fundamentally separate and unrelated to the “real” biological changes underlying organic disease. However, recent breakthroughs in the understanding of the neurobiology of the organism's response to acute and chronic stress, and the evolving understanding of elaborate brain-gut interactions and their modulation in health and disease, are beginning to require a reassessment of chronic stress in the pathophysiology and management not only of functional but also of “organic” gastrointestinal disorders.

Certain stressful life events have been associated with the onset or symptom exacerbation in some of the most common chronic disorders of the digestive system, including functional gastrointestinal disorders (FGD), inflammatory bowel disease (IBD), gastro-oesophageal reflux disease (GORD), and peptic ulcer disease (PUD). Even though methodological differences in reported studies which do and do not support such an association remain to be resolved, the association of sustained stressful life events preceding symptom exacerbation is based on several well designed surveys in patients with FGD,1-4with post-infectious irritable bowel syndrome (IBS),4 and with IBD.5-8 In addition, acute life threatening stress episodes in adult life (rape, post-traumatic stress syndrome) are an important risk factor in the development of functional gastrointestinal disorders.9 Finally, early life stress in the form of abuse plays a major role in the susceptibility of individuals to develop functional as well as IBD10-14 later in life. Thus, depending on the type of stressor, the lag time between the stressful event …
Reducing set-associative cache energy via way-prediction and selective direct-mapping (2001)

Set-associative caches achieve low miss rates for typical applications but result in significant energy dissipation. Set-associative caches minimize access time by probing all the data ways in parallel with the tag lookup, although the output of only the matching way is used. The energy spent accessing the other ways is wasted Eliminating the wasted energy by performing the data lookup sequentially following the tag lookup substantially increases cache access time, and is unacceptable for high-performance L1 caches. In this paper, we apply two previously-proposed techniques, way-prediction and selective direct-mapping, to reducing L1 cache dynamic energy while maintaining high performance. The techniques predict the matching way and probe only the predicted way and not all the ways, achieving energy savings. While these techniques were originally proposed to improve set-associative cache access times, this is the first paper to apply them to reducing cache energy. We evaluate the effectiveness of these techniques in reducing L1 d-cache, L1 i-cache, and overall processor energy. Using these techniques, our caches achieve the energy-delay of sequential access while maintaining the performance of parallel access. Relative to parallel access L1 i- and d-caches, the techniques achieve overall processor energy-delay reduction of 8%, while perfect way-prediction with no performance degradation achieves 10% reduction. The performance degradation of the techniques is less than 3%, compared to an aggressive,.1-cycle, 4-way, parallel access cache.
Stabilization of the Trigonal High-Temperature Phase of Formamidinium Lead Iodide (2015)

Formamidinium lead iodide (FAPbI3) has the potential to achieve higher performance than established perovskite solar cells like methylammonium lead iodide (MAPbI3), while maintaining a higher stability. The major drawback for the latter material is that it can crystallize at room temperature in a wide bandgap hexagonal symmetry (P63mc) instead of the desired trigonal (P3m1) black phase formed at a higher temperature (130 °C). Our results show that employing a mixture of MAI and FAI in films deposited via a two-step approach, where the MAI content is <20%, results in the exchange of FA molecules with MA without any significant lattice shrinkage. Additionally, we show with temperature-dependent X-ray diffraction that the trigonal phase exhibits no phase changes in the temperature range studied (25 to 250 °C). We attribute the stabilization of the structure to stronger interactions between the MA cation and the inorganic cage. Finally, we show that the inclusion of this small amount of MA also has a positive effect on the lifetime of the photoexcited species and results in more efficient devices.
X-ray lithography at ∠100 Å linewidths using x-ray masks fabricated by shadowing techniques (1979)

A new technique for fabricating high contrast x-ray masks with precisely controlled linewidths of less than 100 Å is described. The technique is based on the deposition at an oblique angle (shadowing) of x-ray absorber material onto relief structures of triangular or square cross section in a polyimide plastic membrane. Precise linewidth control is possible because shadowing angle, absorber thickness,and relief structure can be precisely determined. The smooth and well-controlled triangular cross-section structures required are produced in silicon by anisotropic chemical etching and then transferred to polyimide by molding. The square structures are made by reactive-ion-etching of SiO2 with CHF3 and are transferred to polyimide by molding. Results of a numerical model of carbon K (45 Å) x-ray exposures in PMMA of shadowed triangular profile masks are presented which indicate that linewidth control of ±50 Å should be possible for submicrometer period grating. Scanning electron micrographs of PMMA gratings of 1 μm, 3200 Å and 1968 Å period with linewidths as small as 400 Å are shown. The successful replication of ∠200 Å linewidth patterns in PMMA using the carbon K x-ray and shadowed square cross-section masks is reported.
Adipositas und die Entzündung des Fettgewebes (2009)

Adipositas geht mit einer systemischen Entzündungsreaktion einher. Eine Reihe von epidemiologischen Studien hat nachgewiesen, dass erhöhte zirkulierende Entzündungsmarker wie das hoch-sensitiv gemessene C-reaktive Protein (hsCRP) wesentlich zur Insulinresistenz sowie zur Entwicklung von Diabetes mellitus Typ 2 und kardiovaskulären Erkrankungen beitragen. Die systemische Entzündungsreaktion bei Adipositas nimmt ihren Ausgang in erster Linie vom Fettgewebe. Dort kommt es zur Infiltration mit Entzündungszellen, wobei Makrophagen im Vordergrund stehen, aber auch T-Lymphozyten nachgewiesen wurden. Entzündungszellen werden durch Chemokine in das Fettgewebe gelockt. Als Auslöser der Fettgewebsentzündung werden derzeit veränderte Nährstoffflüsse im endoplasmatischen Retikulum der Adipozyten, die zu einer Stressreaktion führen, oxidativer Stress und Hypoxie diskutiert. Eine enge Interaktion von Entzündungszellen und Adipozyten ist für die verminderte Insulinwirkung im Fettgewebe von großer Bedeutung. Durch die Freisetzung inflammatorischer Zytokine wird die Fettgewebsentzündung auch systemisch wirksam. Neue Therapiestrategien, die sich spezifisch gegen die Entzündungsreaktion bei Adipositas richten, könnten wesentlich zur Verringerung der Morbidität adipöser Patienten beitragen.