gebhart/patrepeval huggingface dataset:
Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic (1997)

In the fragile X syndrome, the transition from unmethylated moderate expansions of the CGG repeat (premutations) to methylated large expansions (full mutations) occurs only through maternal transmission. The risk of such transition is highly correlated with the size of the maternal premutation (PM), being very low for small PM alleles (approximately 60 repeats), to 100% for alleles above 100 repeats. The timing of this transition was the object of much speculation. A postzygotic transition was proposed as a preferred model, based on the observation that males with full mutation (FM) have PM in sperm. Analysis of tissues from affected fetuses, including additional data reported here, indicate that such a putative postzygotic transition would have to occur very early in embryogenesis and most likely before determination of germ cell lineage. At least 15% of carriers of a FM show a significant proportion of white blood cells carrying a PM (mutation mosaics). We performed a simulation study showing that, if transition to FM is postzygotic, one should observe a much higher proportion of such mosaics in offspring of mothers with small PMs. This was compared with the actual pattern observed in 212 mutated offspring of 112 PM carrier mothers. We found no effect of maternal PM size on incidence of mosaicism in leucocytes. We propose that this is strong, albeit indirect evidence against a postzygotic transition to FM. A transition at an early morula stage (before day 3) cannot, however, be formally excluded.
Error detection in data base systems (1976)

Incorrect data poses a serious impediment to the effective use of computerized data bases. Conventional approaches to the design and implementation of automated data error detection systems are inadequate for large and complex data bases. Partly, this derives from the inherent intricacy of the problem, with decisions being required as to what checks to perform, how and when to do the checking, and how to respond should an error be found; writing procedures to accomplish these functions is a difficult programming task. Also at fault is the unrealistic and overly simplistic view of data correctness embodied in most contemporary systems.
Localized charge storage in nanocrystal memories: feasibility of a multi-bit cell (2004)

We have realized Si nanocrystal memory cells in which the Si dots have been deposited by chemical vapor deposition (CVD) on the tunnel oxide and then covered by a CVD control oxide. In this paper we report a study on the potential of this type of cell for multi-bit storage. In particular, the possibilities offered by these devices from the point of view of program/erase mechanisms, endurance, and charge retention are shown and discussed.
A fast transient stability screening and ranking tool (2014)

This paper introduces a fast transient stability screening tool to classify a designated set of contingencies into stable and unstable subsets using direct methods. The proposed method is based on the conservativeness of the Lyapunov function. The classification processes of the contingencies are performed along the solution trajectory towards the Controlling Unstable Equilibrium Point (controlling UEP). The proposed screening tool is intended to reliably capture the unstable contingencies and efficiently reduce the number of contingencies that need further analyses. If a numerical problem is encountered during the computation, the proposed scheme applies homotopy-based approaches to find the desired solution. If the numerical problem can not be solved using homotopy-based methods, the contingency is sent to a time-domain simulator for further analysis. The method was applied on the Western System Coordinating Council (WSCC) test system and results are presented.
Structure of the gene coding for the human early lymphocyte activation antigen CD69: A C‐type lectin receptor evolutionarily related with the gene families of natural killer cell‐specific receptors (1994)

CD69 is the earliest inducible cell surface glycoprotein acquired during lymphoid activation. CD69 functions as a signal transmitting receptor involved in cellular activation events including proliferation and the induction of specific genes. This molecule is a member of a supergene family of type-II integral membrane proteins with C-type lectin domains. We have herein studied the genomic structure of the human gene encoding CD69. The coding sequence is divided into five exons separated by four introns. The first two exons corresponded to separate functional domains of the protein (cytoplasmic tail and the transmembrane region), while the final three exons encoded the carbohydrate-recognition domain (CRD). The conserved intron position between the exons encoding the CRD indicated that this protein is closely related to other type-II receptor groups with the C-type CRD, such as the asialoglycoprotein receptors, the low-affinity IgE receptor (CD23), and natural killer cell-specific receptors, NKR-P1 and Ly49. In contrast to the broad NKR-P1 and Ly-49 gene families, CD69 is a single-copy gene, as demonstrated by Southern blot analyses. The major transcription initiation site has been located, by amplification of cDNA 5' ends, 30 nucleotides downstream of a consensus TATA box. Comparison of human CD69 and mouse NKR-P1 gene structures indicates that the first intron maintains a conserved position, suggesting that CD69 and this gene family may diverge from a common ancestor gene. A possible evolutionary pathway of these genes is proposed.
A General Methodology for Data Conversion and Restructuring (1976)

This paper presents a methodology and a model for data conversion or translation. The model assumes that both source and target systems are available and that conversion interfaces may be required to interact between these systems and the conversion system. To achieve data conversion or translation using this approach, two languages are needed: 1) a language to describe the data structures, and 2) a language to specify the mapping between source and target data. This paper describes these two languages, DEFINE and CONVERT and gives numerous examples to show the capabilities of these languages and how they can be used in data conversion and restructuring. Both languages are high level and nonprocedural and have the power to deal with most situations encountered in data conversion processes. In addition, the paper also describes some of the facilities in the languages specifically designed for data checking in a data conversion process.
A new system of sound broadcasting to mobile receivers (2003)

A number of European countries have shown increasing interest in the setting up of a digital sound broadcasting system designed particularly for mobile receivers. The system is intended for domestic hi-fi, portable receivers, and car radios. A system of this type would provide sound quality comparable to compact disk as well as integrating a large number of data broadcasting services. From the technical point of view, the problem is twofold: it requires the development of sophisticated source coding systems, and it requires the design of a channel modulation and coding system that can be used by mobile receivers up to 1 GHz. The general principles, system design, and receiver design are discussed. It is shown that the combination of OFDM (orthogonal frequency-division multiplexing) techniques and concatenated codes provides an elegant solution to the problem of transmitting high rates ( approximately=4.7 Mb/s) in a channel that is strongly affected by multipaths (delay spread up to 16 mu s).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Loss of cone molecular markers in rhodopsin-mutant human retinas with retinitis pigmentosa. (2000)

Even before cones show cytologic changes in response to rod cell degeneration, they lose immunoreactivity for certain cytoplasmic proteins. These cones later show shortening and loss of OS, although their OS membrane proteins remain well labeled. Cones may down regulate expression of both cytoplasmic and outer segment membrane proteins in response to mutant rod cell dysfunction and/or cell death in human RP retinas. Such cytologic and immunocytochemical changes in the cones may presage death of these critical cells in the later stages of RP.
Influence of some commercial proteases and enzymatic associations on the hydrolytic solubilization of deboned poultry meat proteins Influencia de algunas proteasas comerciales y preparados enzimáticos en la solubilización hidrolitica de las proteínas de la carne de pollo separada mecánicamente (2000)

Mechanically deboned poultry meat (MDPM) was used as a basic source of protein to assess the efficiency of seven proteolytic enzymes and some enzymatic associations over the hydrolysis of that protein. As a main parameter, the evolution of protein solubilization during 4 h of proteolysis was evaluated. The enzymes alcalase, esperase, flavourzyme, fungal protease, HT-proteolytic, papain, proteopex, and combinations of alcalase + flavourzyme, esperase + flavourzyme, HT-proteolytic + flavourzyme, and proteopex + flavourzyme were applied at concentrations of 0.60% and 1.20% of commercial product as a function of total protein. The initial pH was adjusted to 7.0 or 8.0 and the temperature was maintained at 50 °C or 60 °C according to optimal conditions for each enzyme. The proteolytic activities of the enzymes were also compared with azocasein. The hydrolysis index (HI), i.e., the rate between the maximum value and the initial amount of soluble protein was formulated to allow the comparison among treatments. Results showed that the temperature did not influence the proteolysis in the tested model. The association of alcalase + flavourzyme was shown to be more efficient than all other treatments, obtaining more than 70% of soluble protein. Fungal protease pre sented the lowest results.
EPA and DHA containing phospholipids have contrasting effects on membrane structure (2021)

Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å<sup>3</sup> vs. Å) were used to determine membrane structure, including membrane width (d-space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0-10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d-space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs.
Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene (2001)

A subpopulation of collie dogs is extremely sensitive to neurotoxicity induced by ivermectin. The aim of this study was to determine the mechanistic basis for this phenomenon. The multi-drug-resistance gene (mdr1) encodes a large transmembrane protein, P-glycoprotein (P-gp), that is an integral part of the blood-brain barrier. P-gp functions as a drug-transport pump at the blood-brain barrier, transporting a variety of drugs from the brain back into the blood. Since ivermectin is a substrate for P-gp, we hypothesized that ivermectin-sensitive collies had altered mdr1 expression compared with unaffected collies. We report a deletion mutation of the mdr1 gene that is associated with ivermectin sensitivity. The 4-bp deletion results in a frame shift, generating several stop codons that prematurely terminate P-gp synthesis. Dogs that are homozygous for the deletion mutation display the ivermectin-sensitive phenotype, while those that are homozygous normal or heterozygous do not display increased sensitivity to ivermectin.
Neuropeptide regulation of feeding in dogs (1991)

Norepinephrine and four families of neuropeptides, namely, neuropeptide Y (NPY), opioid peptides, galanin, and growth hormone-releasing factor (GRH), have been shown to stimulate feeding after central administration. Because these studies were mainly done on laboratory rats, the present study was designed to ascertain the central stimulators of feeding in dogs. We have shown that porcine and human pancreatic polypeptides (PPs), when administered into the third cerebral ventricle (intracerebroventricularly), increased food and water intake of satiated animals but that the COOH-terminal fragments [hPP-(18-36) and hPP-(23-36)] did not do so at the same molar dose (11.9 nmol). The kappa-opioid receptor agonist dynorphin (A-(1-17) also stimulated food and water intake, whereas alpha-neoendorphin and Met-enkephalin did not. These results suggest the structural specificity of PPs and dynorphin peptides for stimulating feeding. Surprisingly, neither intracerebroventricular injections of NPY and peptide YY nor intracerebroventricular pretreatment with anti-hNPY gamma-globulin modulated feeding, stressing the species differences in the feeding response to exogenous substances and the underlying physiology. Intracerebroventricular injections of norepinephrine, GRH, galanin, and pancreastatin also failed to increase food intake, although most substances tended to or did increase water intake. These results suggest that neuropeptides play a role in a species-specific way in modulating appetite regulation.
Recent Advances of Vaccine Adjuvants for Infectious Diseases (2015)

Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.
Heteromultimeric Complexes of CD40 Ligand Are Present on the Cell Surface of Human T Lymphocytes (1997)

CD40 ligand (CD40L), a 33-kDa type II membrane glycoprotein expressed primarily on activated CD4+ T lymphocytes, is responsible for the helper function of T cells on resting B cells in a non-antigen-dependent, non-major histocompatability complex-restricted fashion. Interaction of CD40L with its receptor CD40 induces proliferation of and isotype switching in B lymphocytes. Recently we solved the x-ray structure of recombinant soluble CD40L and showed that, similar to other members of the tumor necrosis factor family, CD40L indeed exists as a trimer. We now report that, under normal physiological conditions, CD40L molecules exist as heteromultimeric complexes. These CD40L complexes, made of the full length and smaller fragments of CD40L, are present on the cell surface of T lymphocytes and are capable of interacting with CD40 molecule. A prominent fragment with a mass of 31 kDa accounts for as much as half of the CD40L on the surface of Jurkat cells. N-terminal sequence data revealed that this fragment lacks the cytoplasmic tail. A minor 18-kDa fragment of CD40L was also characterized which lacks the cytoplasmic tail, transmembrane region, and stalk region of the extracellular domain. The presence of CD40L heteromultimeric variants implies an additional regulation of the functional activity of this ligand complex.
A clinical trial comparing sustained release amitriptyline (Saroten® Retard) and conventional amitriptyline tablets (Saroten®) in endogenously depressed patients with simultaneous determination of serum levels of amitriptyline and nortriptyline (1978)

The clinical effect of a sustained release preparation of amitriptyline has been compared with that of conventional amitriptyline tablets in a double-blind cross-over study with 24 patients suffering from endogenous depression. The sustained release preparation was given in a single evening dose (9 p.m.) of two thirds the total daily dose of conventional tablets, which was given in a three times-a-day regimen (8 a.m., 12 a.m. and 9 p.m.). Serum concentrations of amitriptyline and its active metabolite, nortriptyline, were determined. No difference was found between the two preparations as regards either clinical effect or side effects. No correlation could be shown between the clinical effects and the serum concentrations of amitriptyline and nortriptyline.
Total Synthesis and Biological Evaluation of Amaryllidaceae Alkaloids:  Narciclasine, ent-7-Deoxypancratistatin, Regioisomer of 7-Deoxypancratistatin, 10b-epi-Deoxypancratistatin, and Truncated Derivatives1 (2002)

Biocatalytic approaches have yielded efficient total syntheses of the major Amaryllidaceae alkaloids, all based on the key enzymatic dioxygenation of suitable aromatic precursors. This paper discusses the logic of general synthetic design for lycoricidine, narciclasine, pancratistatin, and 7-deoxypancratistatin. Experimental details are provided for the recently accomplished syntheses of narciclasine, ent-7-deoxypancratistatin, and 10b-epi-deoxypancratistatin via a new and selective opening of a cyclic sulfate over aziridines followed by aza-Payne rearrangement. The structural core of 7-deoxypancratistatin has also been degraded to a series of intermediates in which the amino inositol unit is cleaved and deoxygenated in a homologous fashion. These truncated derivatives and the compounds from the synthesis of the unnatural derivatives have been tested against six important human cancer cell lines in an effort to further develop the understanding of the mode of action for the most active congener in this group, pancratistatin. The results of the biological activity testing as well as experimental, spectral, and analytical data are provided in this manuscript for all relevant compounds.
The Effect of Halogeno Ligands on the Rate of Sulfides Extraction with Transition Metal Complexes (1971)

遷移金属イオンに結合したハロゲンイオンがスルフィドの抽出速度を著しく増大させた。この効果を明らかにするため, 錯体の立体配置が異なる銅 (II) イオン, 亜鉛 (II) イオンおよびカドミウム (II) イオンを用いて,ジメチルスルフィドの錯形成定数を決定した。その結果,kcu2+.(DMS).Br-:kcu2+.cl-:kcu2+.(DMS).clo4-=360:13:1, kzn2+.(DMS).Br-:kzn2+.(DMS).cl-=7:1, kcd2+.(DMS).Br-:kcd2+.(DMS).Cl-=1.5:1 となり, 金属イオン-スルフィド-ハロゲンイオン錯体がとる立体配置により, 各金属イオンの錯形成速度定数が大きく異なることが明らかとなった。平面四配位型の銅 (II) イオンの場合, 電子受容性配位子としてのハロゲンイオンの特性が最も大きくあらわれた。また, ジエチルスルフィドおよび n-プロピルスルフィドと臭化銅 (II), 臭化亜鉛 (II) との錯形成速度を求めた。その結果, 速度はスルフィドの炭素数により大きな影響をうけ, 炭素数が増大するに従って速度が著しく減少していくことを明らかにした。
Application of diazene-directed fragment assembly to the total synthesis and stereochemical assignment of (+)-desmethyl-meso-chimonanthine and related heterodimeric alkaloids (2013)

We describe the first application of our methodology for heterodimerization via diazene fragmentation towards the total synthesis of (-)-calycanthidine, <i>meso</i>-chimonanthine, and (+)-desmethyl-<i>meso</i>-chimonanthine. Our syntheses of these alkaloids feature an improved route to C3a-aminocyclotryptamines, an enhanced method for sulfamide synthesis and oxidation, in addition to a late-stage diversification leading to the first enantioselective total synthesis of (+)-desmethyl-<i>meso</i>-chimonanthine and its unambiguous stereochemical assignment. This versatile strategy for directed assembly of heterodimeric cyclotryptamine alkaloids has broad implications for the controlled synthesis of higher order derivatives with related substructures.
Homeostatic Utility Control (1980)

Distribution Automation and Control (DAC) systems have potentially major effects on costs, social impacts, and even on the nature of the power system itself, especially as dispersed storage, generation, and customer interaction become more prevalent. However, at the present time, it is not clear which particular modes of control will best exploit the capabilities of DAC. Homeostatic Utility Control is an overall concept which tries to maintain an internal equilibrium between supply and demand. Equilibrating forces are obtained over longer time scales (5 minutes and up) by economic principles through an Energy Marketplace using time-varying spot prices. Faster supply-demand balancing is obtained by employing "governor-type" action on certain types of loads using a Frequency Adaptive Power Energy Rescheduler (FAPER) to assist or even replace conventional turbine-governed systems and spinning reserve. Conventional metering is replaced by a Marketing Interface to Customer (MIC) which, in addition to measuring power usage, multiplies that usage by posted price and records total cost. Customers retain the freedom to select their consumption patterns. Homeostatic control is a new, untried concept. It is discussed in this paper because its great potential makes it a vehicle for interesting discussions of where the future may actually evolve.