gebhart/patrepeval huggingface dataset:
Correlation Between Static Foot Type Measurements and Clinical Assessments (2009)

The results of this study indicate the need to measure multiple parameters to assess foot type. However, if only one parameter can be collected, it appears that rearfoot angle explains the majority of variance in the clinically assessed foot type.
AACR Project GENIE: Powering Precision Medicine through an International Consortium (2017)

The AACR Project GENIE is an international data-sharing consortium focused on generating an evidence base for precision cancer medicine by integrating clinical-grade cancer genomic data with clinical outcome data for tens of thousands of cancer patients treated at multiple institutions worldwide. In conjunction with the first public data release from approximately 19,000 samples, we describe the goals, structure, and data standards of the consortium and report conclusions from high-level analysis of the initial phase of genomic data. We also provide examples of the clinical utility of GENIE data, such as an estimate of clinical actionability across multiple cancer types (>30%) and prediction of accrual rates to the NCI-MATCH trial that accurately reflect recently reported actual match rates. The GENIE database is expected to grow to >100,000 samples within 5 years and should serve as a powerful tool for precision cancer medicine.<b>Significance:</b> The AACR Project GENIE aims to catalyze sharing of integrated genomic and clinical datasets across multiple institutions worldwide, and thereby enable precision cancer medicine research, including the identification of novel therapeutic targets, design of biomarker-driven clinical trials, and identification of genomic determinants of response to therapy. <i>Cancer Discov; 7(8); 818-31. ©2017 AACR.</i><i>See related commentary by Litchfield et al., p. 796</i><i>This article is highlighted in the In This Issue feature, p. 783</i>.
Internalization of HIV-1 Tat Requires Cell Surface Heparan Sulfate Proteoglycans (2001)

Tat, the transactivator protein of human immunodeficiency virus-1, has the unusual capacity of being internalized by cells when present in the extracellular milieu. This property can be exploited for the cellular delivery of heterologous proteins fused to Tat both in cell culture and in living animals. Here we provide genetic and biochemical evidence that cell membrane heparan sulfate (HS) proteoglycans act as receptors for extracellular Tat uptake. Cells genetically defective in the biosynthesis of fully sulfated HS are selectively impaired in the internalization of recombinant Tat fused to the green fluorescent protein, as evaluated by both flow cytometry and functional assays. In wild type cells, Tat uptake is competitively inhibited by soluble heparin and by treatment with glycosaminoglycan lyases specifically degrading HS chains. Cell surface HS proteoglycans also mediate physiological internalization of Tat green fluorescent protein released from neighboring producing cells. In contrast to extracellular Tat uptake, both wild type cells and cells genetically impaired in proteoglycan synthesis are equally proficient in the extracellular release of Tat, thus indicating that proteoglycans are not required for this process. The ubiquitous distribution of HS proteoglycans is consistent with the efficient intracellular delivery of heterologous proteins fused with Tat to different mammalian cell types.
Purification, properties, and genetic location of Escherichia coli cytidine 5′-monophosphate N-acetylneuraminic acid synthetase. (1987)

N-Acetylneuraminic acid cytidylyltransferase (EC 2.7.7.43) (CMP-NeuAc synthetase) catalyzes the formation of cytidine monophosphate N-acetylneuraminic acid. We have purified CMP-NeuAc synthetase from an Escherichia coli O18:K1 cytoplasmic fraction to apparent homogeneity by ion exchange chromatography and affinity chromatography on CDP-ethanolamine linked to agarose. The enzyme has a specific activity of 2.1 mumol/mg/min and migrates as a single protein and activity band on nondenaturing polyacrylamide gel electrophoresis. The enzyme has a requirement for Mg2+ or Mn2+ and exhibits optimal activity between pH 9.0 and 10. The apparent Michaelis constants for the CTP and NeuAc are 0.31 and 4 mM, respectively. The CTP analogues 5-mercuri-CTP and CTP-2',3'-dialdehyde are inhibitors. The purified CMP-N-acetylneuraminic acid synthetase has a molecular weight of approximately 50,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The gene encoding CMP-N-acetylneuraminic acid synthetase is located on a 3.3-kilobase HindIII fragment. The purified enzyme appears to be identical to the 50,000 Mr polypeptide encoded by this gene based on insertion mutations that result in the loss of detectable enzymatic activity. The amino-terminal sequence of the purified protein was used to locate the start codon for the CMP-NeuAc synthetase gene. Both the enzyme and the 50,000 Mr polypeptide have the same NH2-terminal amino acid sequence. Antibodies prepared to a peptide derived from the NH2-terminal amino acid sequence bind to purified CMP-NeuAc synthetase.
Insertional inactivation of a chromosomal locus that modulates expression of potential virulence determinants in Staphylococcus aureus (1995)

A single insertion of transposon Tn551 into a unique chromosomal locus of Staphylococcus aureus ISP479C has resulted in a pleiotropic effect on the expression of both extracellular and cell wall proteins. In particular, the expression of cell wall protein A and clumping activity with fibrinogen were rendered undetectable in the mutant 1E3 compared with the parent. The secretion of alpha-hemolysin in mutant 1E3 was modestly increased. Southern blot and phenotypic analyses indicated that this locus is distinct from agr, xpr, and sar, three previously described global regulatory loci. Transduction experiments demonstrated that the genotype associated with mutant 1E3 could be transferred back into the parental strain ISP479C. The transductant 1E3-2 displayed a phenotypic profile similar to that of the original mutant. Northern (RNA) blot studies showed that this locus may be involved in modulating target genes at the mRNA level. In the rabbit endocarditis model, there was a significant decrease in both the infectivity rate and intravegetation bacterial density with mutant 1E3 compared with the parent at an inoculum of 10(3) CFU. Since protein A and the fibrinogen-binding protein(s) are major surface proteins that may mediate bacterial adhesion to host tissues, this locus may be an important genetic element involved in the expression of virulence determinants in S. aureus.
Molecular Mechanisms of Schizophrenia (2007)

Schizophrenia is a complex disorder, where family, twin and adoption studies have been demonstrating a high heritability of the disease and that this disease is not simply defined by several major genes but rather evolves from addition or potentiation of a specific cluster of genes, which subsequently determines the genetic vulnerability of an individual. Linkage and association studies suggest that a genetic vulnerablility, is not forcefully leading to the disease since triggering factors and environmental influences, i.e. birth complications, drug abuse, urban background or time of birth have been identified. This has lead to the assumption that schizophrenia is not only a genetically defined static disorder but a dynamic process leading to dysregulation of multiple pathways. There are several different hypothesis based on several facets of the disease, some of them due to the relatively well-known mechanisms of therapeutic agents. The most widely considered neurodevelopmental hypothesis of schizophrenia integrates environmental influences and causative genes. The dopamine hypothesis of schizophrenia is based on the fact that all common treatments involve antidopaminergic mechanisms and genes such as DRD2, DRD3, DARPP-32, BDNF or COMT are closely related to dopaminergic system functioning. The glutamatergic hypothesis of schizophrenia lead recently to a first successful mGlu2/3 receptor agonistic drug and is underpinned by significant findings in genes regulating the glutamatergic system (SLC1A6, SLC1A2 GRIN1, GRIN2A, GRIA1, NRG1, ErbB4, DTNBP1, DAAO, G72/30, GRM3). Correspondingly, GABA has been proposed to modulate the pathophysiology of the disease which is represented by the involvement of genes like GABRA1, GABRP, GABRA6 and Reelin. Moreover, several genes implicating immune, signaling and networking deficits have been reported to be involved in the disease, i.e. DISC1, RGS4, PRODH, DGCR6, ZDHHC8, DGCR2, Akt, CREB, IL-1B, IL-1RN, IL-10, IL-1B. However, molecular findings suggest that a complex interplay between receptors, kinases, proteins and hormones is involved in schizophrenia. In a unifying hypothesis, different cascades merge into another that ultimately lead to the development of symptoms adherent to schizophrenic disorders.
Enhanced transmission of THz radiation through subwavelength holes (2003)

We present measurements of the transmission of terahertz radiation through periodic arrays of holes made in highly doped silicon wafers. The size of the holes, $70\ifmmode\times\else\texttimes\fi{}70\ensuremath{\mu}\mathrm{m},$ is significantly smaller than the radiation wavelength $\ensuremath{\lambda}\ensuremath{\simeq}500\ensuremath{\mu}\mathrm{m}.$ Sharp resonances and enhanced transmissions are observed. This unusual transmission is attributed to the resonant tunneling of surface-plasmon polaritons that can be excited on doped semiconductors at terahertz frequencies.
Highly conserved sequences in the 3′‐untranslated region of the COL1A1 gene bind cell‐specific nuclear proteins (1991)

Sequencing of the 3' untranslated region (3'-UTR) of the human COL1A1 gene revealed numerous putative regulatory motifs and two highly conserved regions flanking the two polyadenylation sites. The conserved regions were separated by about 700 bp of less conserved sequences. The first region consists of almost all the 3'-UTR of the shorter (4.8 kbp) COL1A1 transcript. The second conserved domain includes a motif shared with several collagen genes. Both conserved domains bind cell-specific nuclear proteins suggesting that the 3'-UTR is important for cell specific expression of the COL1A1 gene.
Guide to molecular cloning techniques. (1987)

This self-contained, state-of-the-art manual is designed to meet the needs of the student, experienced researcher, and newcomer to the molecular biology discipline seeking an efficient means of obtaining a clone. Available in an easy-to-use spiral-bound edition, Guide to Molecular Cloning Techniques progresses from basic techniques underlying much of recombinant DNA technology to a series of sections addressing commonly met problems. Comprehensive protocols are compiled specifically for this volume. Among the topics covered are: Genomic cloning; Preparation and characterization of mRNA cDNA cloning; Screening libraries; Identification and characterization of clones; Methods written by 87 experts; Editors' notes, overviews, and extensive cross-referencing. It includes a Process Guide, a compendium of basic processes in molecular biology indexed for at-a-glance accessibility. It adopts a problem-solving quantitative approach. It places emphasis on strategies for choosing alternative methods.
N-terminal Domains of Human Copper-transporting Adenosine Triphosphatases (the Wilson's and Menkes Disease Proteins) Bind Copper Selectively in Vivo and in Vitro with Stoichiometry of One Copper Per Metal-binding Repeat (1997)

N-terminal domains of the Wilson's and Menkes disease proteins (N-WND and N-MNK) were overexpressed in a soluble form in Escherichia coli as fusions with maltose-binding protein, purified, and their metal-binding properties were characterized. Both N-MNK and N-WND bind copper specifically as indicated by the results of metal-chelate chromatography, direct copper-binding measurements, and chemical modification of Cys residues in the presence of different heavy metals. When E. coli cells are grown in the presence of copper, N-MNK and N-WND bind copper in vivo with stoichiometry of 5-6 nmol of copper/nmol of protein. Copper released from the copper-N-MNK and copper-N-WND complexes reacts with the Cu(I)-selective chelator bicinchoninic acid in the absence of reducing agents. This suggests that in proteins, it is bound in reduced Cu(I) form, in agreement with the spectroscopic properties of the copper-bound domains. Copper bound to the domains in vivo or in vitro specifically protects the N-MNK and N-WND against labeling with the cysteine-directed probe; this indicates that Cys residues in the repetitive motifs GMTCXXCXXXIE are involved in coordination of copper. Direct involvement of the N-terminal domains in the binding of copper suggests their important role in copper-dependent functions of human copper-transporting adenosine triphosphatases (Wilson's and Menkes disease proteins).
Structures of colchicine analogues. IV. An aminodibromoallocolchicine, C20H22Br2N2O4 (1991)

Cristallisation dans C2 avec a=26.331, b=9.472, c=8.311A, β=92.50°, Z=4; affinement jusqu'a R=0.032. Le systeme des cycles biaryl A/C dans cet analogue de la colchicine inactive adopte une configuration anormale R provenant de l'inversion de la conformation du cycle B , caracteristique des colchicinoides
Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine–Phosphoramidite Method (2016)

Stereocontrolled solid-phase synthesis of phosphate/phosphorothioate chimeric oligodeoxyribonucleotides (PO/PS-ODNs) was achieved by integrating the conventional phosphoramidite method into a previously developed oxazaphospholidine method for the stereocontrolled synthesis of P-chiral oligonucleotides. P-Stereodefined PO/PS-ODNs with mixed sequences (up to 12-mers) were obtained in good yields and high stereoselectivities by reacting different combinations of monomers (conventional phosphoramidites/diastereopure nucleoside 3'-O-oxazaphospholidines), activators (ETT/CMPT), capping reagents (Pac2O/CF3COIm), and oxidizing/sulfurizing reagents (TBHP/POS) on an automated synthesizer. A thermal denaturation study examined the resultant diastereopure PO/PS-ODN 12-mers with three consecutive (Rp)- or (Sp)-PS-linkages at the internal or terminal regions of the molecules. We found that (Rp)-PO/PS-ODNs can only moderately destabilize duplexes with complementary oligoribonucleotides (ORNs) compared with their unmodified ODN counterparts (ΔTm = -0.4 °C per modification). In contrast, (Sp)-PO/PS-ODNs have larger destabilizing effects (ΔTm = -1.2 to -0.8 °C per modification). Although smaller destabilizing effects were observed when the (Sp)-PS-linkages were incorporated into the terminal regions of the molecule, there was a weaker correlation between the location of an incorporated (Rp)-PS-linkage and its destabilizing effect.
Crustal structure of central Norway and Sweden from integrated modelling of teleseismic receiver functions and the gravity anomaly (2012)

Receiver functions have been calculated from teleseismic events recorded by an array of seismometers deployed on an E-W transect between the coasts of central Norway and Sweden. Forward and inverse modelling and migration of the receiver functions yields models for the subsurface velocity structure along the profile which have the crust thickening from c. 32 km at the Norwegian coast to c. 43 km beneath the central Scandinavian mountain range and then remaining constant beneath Sweden. There is some evidence for a low-velocity layer in the upper 10 km of the crust beneath parts of Norway and western Sweden and good evidence for a high-velocity lower crust underlying much of Sweden which thins to the west beneath Norway. Inverting the seismic velocities to density results in a very good correspondence between calculated and observed gravity anomalies. The results of this study do not support the presence of a significant crustal root providing buoyant support for the mountain range. Low topography and thick crust beneath Sweden are maintained by the high-velocity, high-density lower crustal layer. The upper crustal low-velocity layer is consistent with models based on existing refraction profiling and known geology and physical properties of the crust. There is no direct correlation between properties of the crust and topography suggesting that recent epeirogenic uplift has not resulted from modification of the crust.
Noncoded residues as building blocks in the design of specific secondary structures: Symmetrically disubstituted glycines and β‐alanine (1993)

Structural changes can be induced in a peptide by selective substitution of coded alpha-amino acid residues by noncoded alpha-amino acid residues and the consequent production of analogues with modified structure and conformational preferences. In this review article we summarize the solid state structural results and the conformational preferences of two classes of "building blocks": (a) the linear and cyclic symmetrically alpha, alpha-disubstituted glycines in which either two identical n-alkyl groups replace the hydrogen atoms of the glycine residue or a cyclic aliphatic side-chain system is formed by linking the two alpha-carbon side chains, respectively; and (b) the beta-alanine residue. Examples, whenever possible, of the use of these residues for the elucidation of the bioactive conformation in the appropriate biological systems will be given.
Vascular Endothelial Genes That Are Responsive to Tumor Necrosis Factor- In Vitro Are Expressed in Atherosclerotic Lesions, Including Inhibitor of Apoptosis Protein-1, Stannin, and Two Novel Genes (1999)

Activation and dysfunction of endothelial cells play a prominent role in patho-physiological processes such as atherosclerosis. We describe the identification by differential display of 106 cytokine-responsive gene fragments from endothelial cells, activated by monocyte conditioned medium or tumor necrosis factor-alpha. A minority of the fragments (22/106) represent known genes involved in various processes, including leukocyte trafficking, vesicular transport, cell cycle control, apoptosis, and cellular protection against oxidative stress. Full-length cDNA clones were obtained for five novel transcripts that were induced or repressed more than 10-fold in vitro. These novel human cDNAs CA2_1, CG12_1, GG10_2, AG8_1, and GG2_1 encode inhibitor of apoptosis protein-1 (hIAP-1), homologues of apolipoprotein-L, mouse rabkinesin-6, rat stannin, and a novel 188 amino acid protein, respectively. Expression of 4 novel transcripts is shown by in situ hybridization on healthy and atherosclerotic vascular tissue, using monocyte chemotactic protein-1 as a marker for inflammation. CA2_1 (hIAP-1) and AG8_1 are expressed by endothelial cells and macrophage foam cells of the inflamed vascular wall. CG12_1 (apolipoprotein-L like) was specifically expressed in endothelial cells lining the normal and atherosclerotic iliac artery and aorta. These results substantiate the complex change in the gene expression pattern of vascular endothelial cells, which accompanies the inflammatory reaction of atherosclerotic lesions.
<title>Vertical-cavity surface-emitting laser arrays</title> (1995)

This paper reviews the state-of-the-art performance of producible, 850-nm, current-guided GaAs/AlGaAs, top-emitting vertical-cavity surface-emitting lasers (VCSELs) and arrays. We focus on the flexibility of this technology platform in demonstrating a variety of devices and arrays. This includes a 99.8% device yield across a 3-in-dia. Metal-Organic Vapor Phase Epitaxy (MOVPE)-grown wafer and wavelength operation across approximately equals 100-nm range. Recent progress in device performance (V<SUB>th</SUB> equals 1.55 V; I<SUB>th</SUB> equals 0.68 mA; P<SUB>cw</SUB> equals 59 mW; T<SUB>cw</SUB> equals 200 degree(s)C, (eta) <SUB>wp</SUB> equals 28%) have and will enable great advances in VCSEL-array-based technologies. Included are unique ways of engineering modal characteristics from single-mode to quasi-incoherent emission. Array applications include 1D addressable arrays, particularly in the area of high-speed optical data links. An example application is the 32-channel-wide Optoelectronic Technology Consortium parallel links that have been operated error-free up to 980 Mbit/s (Manchester coded) through 100 m of bier. Two-dimensional matrix-addressable VCSEL arrays for processing and imaging applications will also be reviewed. Finally, we will discuss the exploitation of this VCSEL technology to explore the use of patterned or phased arrays of VCSELs. Their performance and relevant physics will be described, including the recent demonstration of in-phase coupling, watt-level emission, and multi-transverse-element mode coupling.
Stimulation of endothelial cell prostacyclin formation by interleukin-2. (1986)

The production of prostacyclin (PGI2) by the luminal surface of bovine aorta was significantly increased when incubated with 1 unit of interleukin-2 (IL-2). In separate experiments, confluent cultured bovine aortic endothelial cells were also shown to be stimulated to produce increased levels of PGI2 in a concentration-dependent manner by purified IL-2. This increase in prostacyclin biosynthesis was inhibited by cycloheximide. Since the recovery of prostacyclin production in aspirin treated cells was stimulated by interleukin-2, our results suggest that the stimulatory effect of interleukin-2 on prostacyclin synthesis is at least partially mediated by the de novo synthesis of cyclooxygenase.
Substrate Specificity Determinants of the Methanogen Homoaconitase Enzyme: Structure and Function of the Small Subunit, (2010)

The aconitase family of hydro-lyase enzymes includes three classes of proteins that catalyze the isomerization of alpha-hydroxy acids to beta-hydroxy acids. Besides aconitase, isopropylmalate isomerase (IPMI) proteins specifically catalyze the isomerization of alpha,beta-dicarboxylates with hydrophobic gamma-chain groups, and homoaconitase (HACN) proteins catalyze the isomerization of tricarboxylates with variable chain length gamma-carboxylate groups. These enzymes' stereospecific hydro-lyase activities make them attractive catalysts to produce diastereomers from unsaturated precursors. However, sequence similarity and convergent evolution among these proteins lead to widespread misannotation and uncertainty about gene function. To find the substrate specificity determinants of homologous IPMI and HACN proteins from Methanocaldococcus jannaschii, the small-subunit HACN protein (MJ1271) was crystallized for X-ray diffraction. The structural model showed characteristic residues in a flexible loop region between alpha2 and alpha3 that distinguish HACN from IPMI and aconitase proteins. Site-directed mutagenesis of MJ1271 produced loop-region variant proteins that were reconstituted with wild-type MJ1003 large-subunit protein. The heteromers formed promiscuous hydro-lyases with reduced activity but broader substrate specificity. Both R26K and R26V variants formed relatively efficient IPMI enzymes, while the T27A variant had uniformly lower specificity constants for both IPMI and HACN substrates. The R26V T27Y variant resembles the MJ1277 IPMI small subunit in its flexible loop sequence but demonstrated the broad substrate specificity of the R26V variant. These mutations may reverse the evolution of HACN activity from an ancestral IPMI gene, demonstrating the evolutionary potential for promiscuity in hydro-lyase enzymes. Understanding these specificity determinants enables the functional reannotation of paralogous HACN and IPMI genes in numerous genome sequences. These structural and kinetic results will help to engineer new stereospecific hydro-lyase enzymes for chemoenzymatic syntheses.