gebhart/patrepeval huggingface dataset:
Direct molecular haplotyping by melting curve analysis of hybridization probes: beta 2-adrenergic receptor haplotypes as an example (2005)

Direct determination of the association of multiple genetic polymorphisms, or haplotyping, in individual samples is challenging because of chromosome diploidy. Here, we describe the ability of hybridization probes, commonly used as genotyping tools, to establish single nucleotide polymorphism (SNP) haplotypes in a single step. Three haplotypes found in the beta 2-adrenergic receptor (beta2AR) gene and characterized by three different SNPs combinations are presented as examples. Each combination of SNPs has a unique stability, recorded by its melting temperature, even when intervening sequences from the template must loop out during probe hybridization. In the course of this study, two haplotypes in beta2AR not described previously were discovered. This approach provides a tool for molecular haplotyping that should prove useful in clinical molecular genetics diagnostics and pharmacogenetic research where methods for direct haplotyping are needed.
CD40 Ligand Mutants Responsible for X-linked Hyper-IgM Syndrome Associate with Wild Type CD40 Ligand (1999)

CD40 ligand (CD40L) is a 33-kDa type II membrane glycoprotein mainly expressed on activated CD4(+) T cells in trimeric form. When it is mutated, the clinical consequences are X-linked hyper-IgM syndrome (XHIM), a primary immunodeficiency disorder characterized by low levels of IgG, IgA, and elevated or normal levels of IgM. Mutated CD40L can no longer bind CD40 nor provide signals for B cells to proliferate and to switch from IgM to other immunoglobulin isotypes. When considering gene therapy for XHIM, it is important to address the possibility that the mutated CD40L associates with transduced wild type CD40L, and as a consequence, immune reconstitution is not attained. In this study, we demonstrate that the various mutated CD40L species we have identified in patients with XHIM, including both full-length and truncated mutants, associate with wild type CD40L on the cell surface of co-transfected COS cells. The association between wild type and mutated CD40L was also observed in CD4(+) T cell lines established from XHIM patients with leaky splice site mutations. The clinical phenotype of these patients suggests that this association between wild type and mutated CD40L species may result in less efficient cross-linking of CD40.
Perspectives on Vacuum-Assisted Closure Therapy in Pilonidal Sinus Surgery (2005)

Diseases of the Colon & Rectum: September 2005 - Volume 48 - Issue 9 - p 1829 doi: 10.1007/s10350-005-0109-6
Integrating XML data in the TARGIT OLAP system (2004)

We present work on logical integration of OLAP and XML data sources, carried out in cooperation between TARGIT, a Danish OLAP client vendor, and Aalborg University. A prototype has been developed that allows XML data on the WWW to be used as dimensions and measures in the OLAP system in the same way as ordinary dimensions and measures, providing a powerful and flexible way to handle unexpected or short-term data requirements as well as rapidly changing data. Compared to earlier work, we present several major extensions that resulted from TARGIT's requirements. These include the ability to use XML data as measures, as well as a novel multigranular data model and query language that formalizes and extends the TARGIT data model and query language.
STRUCTURE AND RHEOLOGICAL FUNCTION OF SIDE BRANCHES OF CARBOHYDRATE POLYMERS (1991)

ABSTRACT This review consists of two major parts: (1) the rheological theories of branched polymers and (2) the structural features of side branches of carbohydrates and their effects on the rheological properties. The rheological properties influenced by branching are discussed in terms of radius of gyration, intrinsic viscosity, zero‐shear viscosity (η o ), elastic properties represented by the zero‐shear recoverable compliance (J e o ), shear rate dependence of viscosity, extensional viscosity and thermal sensitivity of viscosity. The second part is focused on the structural characteristics of side branches found in four typical branched carbohydrates, i.e., starch (amylopectin), galactomannan, xanthan and pectin, with an emphasis on their contribution to the rheological properties.
A new model for broadband waveguide to microstrip transition design (1986)

A new model is presented which permits the prediction of the resonant frequencies created by antipodal finline waveguide to microstrip transitions. The transition is modeled as a tapered transmission line in series with an infinite set of coupled resonant circuits. The resonant circuits are modeled as simple microwave resonant cavities of which the resonant frequencies are easily determined. The model is developed and the resonant frequencies determined for several different transitions. Experimental results are given to confirm the models.
SSBI Cancellation Based on Time Diversity Reception in SSB-DD-OOFDM Transmission Systems (2014)

A novel SSBI cancellation scheme based on time diversity reception is proposed. Experiment shows that the proposed scheme improves ~3.6dB sensitivity compared with baseband optical OFDM scheme in a 5-Gbps SSB-DD-OOFDM system over 100-km SMF.
Changes in the Electronic Properties of a Molecule When It Is Wired into a Circuit (2002)

Molecular electronic devices require at least two electrical contacts to one (or more) molecule(s). Single molecules are reliably probed by bonding one end to a gold substrate and the other end to a gold nanocrystal. The circuit is completed with a gold-coated atomic force microscope probe. Measurements of the decay of electronic current with the length of n-alkanedithiol molecules in these single-molecule nanojunctions are reported as a function of the applied bias. The value of the decay constant near zero bias was obtained from measurements in the ohmic region of the current−voltage curves. The electron tunneling decay rate is significantly smaller (βN = 0.57 ± 0.03) than observed for molecules bonded at just one end (βN ≈ 1), and it falls to even smaller values as the applied bias is increased. Both these effects are quantitatively accounted for by a large shift in molecular levels caused by the attachment of wires at each end.
Synthesis and Structure-Activity Relationships of 7-(3-(1-Aminoalkyl)pyrrolidinyl)- and 7-(3-1-aminocycloalkyl)pyrrolidinyl)quinolone Antibacterials. (1994)

A series of 7-[3-(1-aminoalkyl and 1-aminocycloalkyl)-1-pyrrolidinyl] quinolones have been prepared and their biological properties evaluated. Among them, 1-(S)-aminoalkyl derivatives exhibited potent antibacterial activities against gram-positive and gram-negative organisms. They had moderate lipophilicity and high aqueous solubility compared to their aminomethyl counterparts; e.g., the 3-(1-aminoethyl)-1-pyrrolidinyl compound (83) showed superior pharmacokinetic properties to its aminomethyl counterpart (6).
Zur weiteren Kenntnis des Chlorophylls und des Hämins, VI. Formylierung der meso‐Kohlenstoffatome von Alkyl‐substituierten Porphyrinen (1966)

Abstract Durch Reduktion der Methoxycarbonylgruppen des Mesoporphyrin‐dimethylesters ( 4a ) wird das bisher unbekannte 1.3.5.8‐Tetramethyl‐2.4‐diäthyl‐6.7‐dipropyl‐porphin ( 5c ) erhalten. 5c läßt sich wie Octaäthyloporphin ( 7a ) als Kupferkomplex mit Hilfe der Vilsmeier‐Reaktion an einem meso ‐Kohlenstoffatom formylieren. Aus dem hierbei entstandenen Gemisch von vier Isomeren kann eines durch Chromatographie abgetrennt und auf Grund seines NMR‐Spektrums als γ‐Formyl‐1.3.5.8‐tetramethyl‐2.4‐diäthyl‐6.7‐dipropyl‐porphin ( 6a ) identifiziert werden. Durch Reduktion des meso ‐Formyl‐octaäthylporphins 7b und durch Wasser‐Abspaltung aus dessen Oxim ( 7d ) werden meso ‐Hydroxymethyl‐octaäthylporphin 7f und meso ‐Cyan‐octaäthylporphin 7e dargestellt. Der Einfluß von meso ‐Substituenten auf die Elektronen‐ und NMR‐Spektren wird diskutiert.
Conditional Ablation of Cerebellar Astrocytes in Postnatal Transgenic Mice (1996)

Astrocytes have been proposed to have multiple roles in the development and maintenance of the vertebrate CNS. To facilitate documentation of these roles, we designed a transgene to enable their ablation at selectable times. The transgene consists of the coding region for the herpes simplex virus-thymidine kinase (HSV-TK) under the control of the human glial fibrillary acidic protein gene promoter. The HSV-TK is innocuous but converts the antiherpetic agent ganciclovir (GCV) to a toxic product that interferes with DNA replication in proliferating cells. In a developmental study, transgenic mice were treated with GCV during the first postnatal week, with evaluation at P19. Treated mice displayed severe ataxia. Histological examination revealed disrupted astrocyte development, particularly in the cerebellum, with marked secondary effects on other cell types. Cerebellar defects included a loss in the numbers of astrocytes and an overall reduction in cerebellar size and disruption of the normally well defined cellular layers. Radial glia were disordered, Purkinje cells were ectopically distributed and displayed abnormal dendritic trees, and granule cells were markedly depleted. These effects were more severe in animals treated on postnatal day 1 versus treatment at day 5. A major factor causing granule cell death was excitotoxicity attributable to activation of NMDA receptors. These results suggest a critical role for astrocytes in cerebellar development.
S3: The IBM Smart Surveillance System: From Transactional Systems to Observational Systems (2007)

Pervasive sensor based systems are transforming Information Technology systems from being transactional in nature to being observational in nature. Observational systems are inherently distributed and capture information at a much finer grain of space and time. Enabling and building such systems also poses many technology challenges, extracting information from sensor signals, indexing and searching sensor meta-data, data mining and scalability. In this paper we use S3: the IBM smart surveillance system as an example of an observational system to explore several of these issues through real world deployment examples.
Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays. (2001)

It is now clear that aberrant DNA methylation observed in cancer cells is not restricted to a few CpG islands, but affects multiple loci. When this epigenetic event occurs at the 5'-end of the regulatory region of genes, it is frequently associated with transcriptional silencing. To investigate further this widespread event in the tumor genome, we developed a novel microarray containing 7776 short GC-rich tags tethered to glass slide surfaces. This DNA chip was used to study 17 paired tissues of breast tumors and normal controls. Amplicons, representing differential pools of methylated DNA fragments between tumors and normal controls, were cohybridized to the microarray panel. Hypermethylation of multiple CpG island loci was then detected in a two-color fluorescence system. Approximately 1% (on average, 83 loci) of these CpG islands examined were hypermethylated in this patient group. Hierarchical clustering segregated these tumors based on their methylation profiles and identified a group of CpG island loci that corresponds to the hormone-receptor status of breast cancer. This observation was independently confirmed by examining a single locus, the promoter of the human glypican 3 gene, which was predominately hypermethylated in the hormone receptor-negative tumors. Our findings support the notion that hypermethylation of critical CpG island loci influences cancer development and produces distinct epigenetic signatures for particular tumor subtypes.
A Class of Algorithms for Fast Digital Image Registration (1972)

The automatic determination of local similarity between two structured data sets is fundamental to the disciplines of pattern recognition and image processing. A class of algorithms, which may be used to determine similarity in a far more efficient manner than methods currently in use, is introduced in this paper. There may be a saving of computation time of two orders of magnitude or more by adopting this new approach. The problem of translational image registration, used for an example throughout, is discussed and the problems with the most widely used method-correlation explained. Simple implementations of the new algorithms are introduced to motivate the basic idea of their structure. Real data from ITOS-1 satellites are presented to give meaningful empirical justification for theoretical predictions.
α/β–T Cell Receptor (TCR)+CD4−CD8− (NKT) Thymocytes Prevent Insulin-dependent Diabetes Mellitus in Nonobese Diabetic (NOD)/Lt Mice by the Influence of Interleukin (IL)-4 and/or IL-10 (1998)

We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in alpha/beta-T cell receptor (TCR)+CD4-CD8- NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM in NOD mice was studied by the infusion of thymocyte subsets into young female NOD mice. A single intravenous injection of 10(6) CD4-/lowCD8- or CD4-CD8- thymocytes from female (BALB/c x NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. Insulitis was still present in some recipient mice, although the cell infiltrates were principally periductal and periislet, rather than the intraislet pattern characteristic of insulitis in unmanipulated NOD mice. Protection was not associated with the induction of "allogenic tolerance" or systemic autoimmunity. Accelerated IDDM occurs after injection of splenocytes from NOD donors into irradiated adult NOD recipients. When alpha/beta-TCR+ and alpha/beta-TCR- subsets of CD4-CD8- thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the alpha/beta-TCR+ population was protective, confirming that NKT cells were responsible for this activity. The protective effect in the induced model of IDDM was neutralized by anti-IL-4 and anti-IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. These results have significant implications for the pathogenesis and potential prevention of IDDM in humans.
Yeast and its Importance to Wine Aroma - A Review (2019)

Wine aroma; wine flavour; fermentation bouquet; wine yeast
<title>New near-infrared dyes for applications in bioanalytical methods</title> (1995)

The near infrared (NIR) fluorescence has several advantages as a detection system over visible or uv fluorescence counterpart. The spectral properties of cyanine dyes offer advantages for detection in the longer wavelength NIR region. The present work focuses on the synthesis of NIR dyes and their applications in bioanalytical chemistry. Several cyanine dyes have been synthesized. The spectroscopic characteristics such as molar absorptivity, fluorescence quantum yield, excitation and emission maxima have been determined. The potential utilities of these new dyes as probe and reporter molecules in bioanalytical methods have been explored. Dyes bearing reactive functional groups such as isothiocyanate, carboxylic acid or hydroxyl groups can be directly used for covalent labeling of proteins and nucleic acids. Their importance in the synthesis of dye labeled phosphoramidites and dye labeled dideoxynucleotides and use in DNA sequencing have been evaluated.
cDNAs encoding the large subunit of human replication factor C. (1993)

Replication factor C (RFC) is a multisubunit, DNA polymerase accessory protein required for the coordinated synthesis of both DNA strands during simian virus 40 DNA replication in vitro. Previous studies have shown that RFC is a DNA-dependent ATPase that binds in a structure-specific manner to the 3' end of a primer hybridized to a template DNA, an activity thought intrinsic to the 140-kDa component of this multisubunit complex. Here, the isolation and analysis of cDNAs encoding this subunit is described. Analysis of the full-length coding sequence revealed an open reading frame of 3.4 kb, encoding an 1148-amino acid protein with a predicted molecular mass of 130 kDa. A putative ATP-binding motif was observed that is similar to a motif in several of the smaller subunits of RFC and in functionally homologous replication factors of bacterial and viral origin. A "DEAD" box is also conserved among these proteins. The predicted protein shows significant identity with a DNA-binding protein of murine origin (B. Luckow, P. Lichter, and G. Schütz, personal communication). Regions of similarity were also seen between the amino acid sequences of the 140-kDa subunit of RFC, poly(ADP-ribose) polymerase, and bacterial DNA ligases--possibly representing a conserved structural feature of these proteins that bind similar DNA substrates.
Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. (1999)

In humans, 80-90% of an administered dose of 5-fluorouracil (5-FU) is degraded by dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2), the initial rate-limiting enzyme in pyrimidine catabolism. Cancer patients with decreased DPD activity are at increased risk for severe toxicity including diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity, and, in some cases, death. We now report the first known cancer patient who developed life-threatening complications after treatment with topical 5-FU and was shown subsequently to have profound DPD deficiency. RT-PCR and genomic PCR methodologies were used to identify a G to A mutation in the GT 5' splicing recognition sequence of intron 14, resulting in a 165-bp deletion (corresponding to exon 14) in this patient's DPD mRNA. Immunoprecipitation and Western blot analysis were then used to demonstrate that the aberrant DPD mRNA is translated into a nonfunctional DPD protein that is ubiquitinated. We conclude that the presence of this metabolic defect combined with topical 5-FU (a drug demonstrating a narrow therapeutic index) results in the unusual presentation of life-threatening toxicity after treatment with a topical drug. These data further suggest that degradation by the ubiquitin-proteosome-mediated system plays a role in the elimination of the DPD protein.
Purification of Active E1α2β2 of Pseudomonas Putida Branched‐Chain‐Oxoacid Dehydrogenase (1995)

Active E1 component of Pseudomonas putida branched-chain-oxoacid dehydrogenase was purified from P. putida strains carrying pJRS84 which contains bkdR (encoding the transcriptional activator) and bkdA1 and bkdA2 (encoding the alpha and beta subunits). Expression was inducible, however, 45-, 39- and 37-kDa proteins were produced instead of the expected 45-kDa and 37-kDa proteins. The 45-kDa protein was identified as E1 alpha and the 37-kDa and 39-kDa proteins were identified as separate translational products of bkdA2 by their N-terminal sequences. The N-terminal amino acid of the 39-kDa protein was leucine instead of methionine. The 45-, 39- and 37-kDa proteins were also produced in wild-type P.putida. Translation of bkdA1 and bkdA2 from an Escherichia coli expression plasmid produced only 45-kDa and 39-kDa proteins, with N-terminal methionine on the 39-kDa protein. The insertion of guanine residues 5' to the first ATG of bkdA2 did not affect expression of E1 beta in P. putida including the N-terminal leucine which appears to eliminate the possibility of ribosome jumping. The Z-average molecular mass of the E1 component was determined by sedimentation equilibrium to be 172 +/- 9 kDa compared to a calculated value of 166 kDa for the heterotetramer and a Stokes radius of 5.1 nm. E1 alpha Ser313, which is homologous to the phosphorylated residue of rat liver E1 alpha, was converted to alanine resulting in about a twofold increase in Km, but no change in Kcat. S315A and S319A mutations had no effect on Km or Kcat indicating that these residues do not play a major part in catalysis of E1 alpha beta 2.
CNDO/S-CI Calculations of some Carbonyl-containing Organic Luminophores with a Stilbene Subchromophore (1985)

For a series of carbonyl-containing compounds with a stilbene subchromophore the lowest ten singlet and triplet states have been calculated with the aid of the CNDO/S-CI method. The results were used to rationalize the relative ordering of the lowest-lying S(ππ*), S(ππ*), T(ππ*), and T(ππ*) electronic states. Using the calculated energy separation between the singlet ππ*and nπ* states and between the singlet ππ* and triplet nπ* states the fluorescence ability of the compounds studied is interpreted. The connection between the structure of the compounds and their fluorescence is discussed. It is shown that an increase of the solvent polarity in some cases may lead to an inversion of the singlet nπ* and ππ* levels and to an enhancement of the fluorescence quantum yield.
Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins (2001)

Despite the benefits of currently available preventative and therapeutic interventions, atherosclerotic vascular disease continues to be a major cause of morbidity and mortality in much of the Western World. This emphasize,,, the need for additional preventive and therapeutic interventions exploiting new targets to compliment and augment the results of LDL lowering and other current strategies. One such potential target is HDL and its apolipoproteins, A large body of experimental evidence suggests that augmenting the levels and/or function of HDL and its apolipoproteins can have major vascular protective effects ranging from prevention to stabilization and regression, independent of total or non-HDL cholesterol levels. Therefore, we think that the time is ripe for the development and clinical testing of this new frontier in antiatherogenic strategy. In the present article, We will review the structure/function of HDL and explore means of enhancing the levels and/or function of HDL and its apolipoproteins for vascular protection.
Structural Characterization and Kinetics of Nitric-oxide Synthase Inhibition by Novel N5-(Iminoalkyl)- and N5-(Iminoalkenyl)-ornithines (2003)

Isoform-specific nitric-oxide synthase (NOS) inhibitors may prove clinically useful in reducing the pathophysiological effects associated with increased neuronal NOS (nNOS) or inducible NOS (iNOS) activity in a variety of neurological and inflammatory disorders. Analogs of the NOS substrate L-arginine are pharmacologically attractive inhibitors because of their stability, reliable cell uptake, and good selectivity for NOS over other heme proteins. Some inhibitory arginine analogs show significant isoform selectivity although the structural or mechanistic basis of such selectivity is generally poorly understood. In the present studies, we determined by x-ray crystallography the binding interactions between rat nNOS and N5-(1-imino-3-butenyl)-L-ornithine (L-VNIO), a previously identified mechanism-based, irreversible inactivator with moderate nNOS selectivity. We have also synthesized and mechanistically characterized several L-VNIO analogs and find, surprisingly, that even relatively minor structural changes produce inhibitors that are either iNOS-selective or non-selective. Furthermore, derivatives having a methyl group added to the butenyl moiety of L-VNIO and L-VNIO derivatives that are analogs of homoarginine rather than arginine display slow-on, slow-off kinetics rather than irreversible inactivation. These results elucidate some of the structural requirements for isoform-selective inhibition by L-VNIO and its related alkyl- and alkenyl-imino ornithine and lysine derivatives and may provide information useful in the ongoing rational design of isoform-selective inhibitors.