gebhart/patrepeval huggingface dataset:
The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells (2007)

Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC) patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing potential of bortezomib in NSCLC cells was found to be dependent not only on the apoptotic phenotype but also on the proteasomal phenotype of individual cell lines. Upon effective proteasome inhibition, H460 cells were more susceptible to apoptosis induction by bortezomib than SW1573 cells, indicating a different apoptotic phenotype. However, exposure to a low dose of bortezomib did only result in SW1573 cells, and not in H460 cells, in inhibition of proteasome activity and subsequent apoptosis. This suggests a different proteasomal phenotype as well. Additionally, overexpression of anti-apoptotic protein Bcl-2 in H460 cells did not affect the proteasomal phenotype of H460 cells but did result in decreased bortezomib-induced apoptosis. In conclusion, successful proteasome-inhibitor based treatment strategies in NSCLC face the challenge of having to overcome apoptosis resistance as well as proteasomal resistance of individual lung cancer cells. Further studies in NSCLC are warranted to elucidate underlying mechanisms.
Cholesterol 24-Hydroxylase: An Enzyme of Cholesterol Turnover in the Brain (2009)

Cholesterol 24-hydroxylase is a highly conserved cytochrome P450 that is responsible for the majority of cholesterol turnover in the vertebrate central nervous system. The enzyme is expressed in neurons, including hippocampal and cortical neurons that are important for learning and memory formation. Disruption of the cholesterol 24-hydroxylase gene in the mouse reduces both cholesterol turnover and synthesis in the brain but does not alter steady-state levels of cholesterol in the tissue. The decline in synthesis reduces the flow of metabolites through the cholesterol biosynthetic pathway, of which one, geranylgeraniol diphosphate, is required for learning in the whole animal and for synaptic plasticity in vitro. This review focuses on how the link between cholesterol metabolism and higher-order brain function was experimentally established.
ATM network and VBR video source: data structure and statistical analysis of an implemented hybrid DCT broadcast video encoder (2002)

The arrangement of data in a variable bit rate (VBR) video codec, making it suitable for the transmission over ATM (asynchronous transfer mode) networks, is addressed. Attention is focused on two aspects specifically belonging to the ATM environment: the impairment due to the loss of ATM data cells and the statistical analysis of a real VBR video source. A particular implementation of a hybrid DCT (discrete cosine transform) broadcast video codec, which adheres to the recent specifications proposed by the European Telecommunications Standards Institute, is addressed. In order to optimize the performance with respect to cell losses, a specific solution based on the concept of organizing data into video packets is explored. The statistical characteristics of the available VBR video source are investigated, using a real-time acquisition system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthetic α-Subunit Peptides Stimulate Testosterone Productionin Vitroby Rat Leydig Cells* (1990)

The glycoprotein hormones (LH, hCG, FSH, and TSH) have a common 92-amino acid alpha-subunit which is noncovalently linked to a hormone-specific beta-subunit. Synthetic peptides of the alpha-subunit have been shown to inhibit binding of [125I]iodo-hCG to rat ovarian membrane and [125I]iodo-TSH to human thyroid membrane preparations. Synthetic overlapping peptides of the alpha-subunit of hCG were prepared by solid phase techniques and tested in a standard in vitro rat Leydig cell bioassay. Three regions in the alpha-subunit (alpha 1-15, alpha 30-45, and alpha 71-85) were found to stimulate testosterone production. All three regions correlate with inhibition of hCG binding to ovarian receptors, but subtle differences exist between the binding sites and effector sites. These data indicate that the glycoprotein alpha-subunit has intrinsic bioactivity.
Platelet-derived growth factor causes pulmonary cell proliferation and collagen deposition in vivo. (1996)

Platelet-derived growth factor (PDGF) is postulated to play a role in the pathophysiology of pulmonary fibrosis. Recombinant human PDGF-BB administered as a single intratracheal injection in rats causes an increase in peribronchial and perivascular stromal cells on days 2 and 3 after injection as evaluated by hematoxylin and eosin histology and 5-bromodeoxyuridine incorporation. Proliferation of bronchial epithelial cells and arterial smooth muscle cells, although not evident by routine histological examination alone, is detected on days 2 and 3 by increased 5-bromodeoxyuridine incorporation. A mild increase in 5-bromodeoxyuridine labeling is observed in peripheral alveolar parenchyma after injection of PDGF. The proliferative peribronchial and perivascular mesenchymal cells appear by light microscopic and ultrastructural criteria to be fibroblasts that are immunoreactive for vimentin but negative for alpha-smooth muscle actin and desmin. Daily intratracheal injection of PDGF-BB for 3 days causes a slightly more pronounced peribronchial and perivascular spindle cell proliferation accompanied by collagen deposition as evaluated by Masson's trichrome stain. PDGF-induced increases in cellularity and collagen resolve within 5 days after the last PDGF injection. In conclusion, intratracheal injection of PDGF-BB causes transient proliferation of pulmonary mesenchymal and epithelial cells accompanied by collagen deposition.
Nucleotide sequence of the Shiga-like toxin genes of Escherichia coli. (1987)

We have determined the nucleotide sequence of the sltA and sltB genes that encode the Shiga-like toxin (SLT) produced by Escherichia coli phage H19B. The amino acid composition of the A and B subunits of SLT is very similar to that previously established for Shiga toxin from Shigella dysenteriae 1, and the deduced amino acid sequence of the B subunit of SLT is identical with that reported for the B subunit of Shiga toxin. The genes for the A and B subunits of SLT apparently constitute an operon, with only 12 nucleotides separating the coding regions. There is a 21-base-pair region of dyad symmetry overlapping the proposed promoter of the slt operon that may be involved in regulation of SLT production by iron. The peptide sequence of the A subunit of SLT is homologous to the A subunit of the plant toxin ricin, providing evidence for the hypothesis that certain prokaryotic toxins may be evolutionarily related to eukaryotic enzymes.
Synergistic Effect of Zanamivir−Porphyrin Conjugates on Inhibition of Neuraminidase and Inactivation of Influenza Virus (2009)

New anti-influenza agents of tetravalent zanamivir on a porphyrin scaffold were synthesized. These compounds are 10 to 100 times more potent in inhibiting influenza replications even though they are somewhat less potent in neuraminidase inhibition than the monomeric zanamivir. The enhanced anti-influenza activity is probably attributable to the additional viral inactivation by singlet oxygen due to sensitization of the porphyrin moiety, which is brought in close proximity of virus by the conjugated zanamivir in a manner resembling the "magic bullet" mechanism.
Newborn Screening Fact Sheets (2006)

Newborn screening fact sheets were last revised in 1996 by the American Academy of Pediatrics Committee on Genetics. This revision was prompted by advances in the field since 1996, including technologic innovations, as well as greater appreciation of ethical issues such as those surrounding informed consent. The following disorders are discussed in this revision of the newborn screening fact sheets: biotinidase deficiency, congenital adrenal hyperplasia, congenital hearing loss, congenital hypothyroidism, cystic fibrosis, galactosemia, homocystinuria, maple syrup urine disease, medium-chain acyl-coenzyme A dehydrogenase deficiency, phenylketonuria, sickle cell disease and other hemoglobinopathies, and tyrosinemia. A series of topics related to newborn screening is discussed in a companion publication to this electronic publication of the fact sheets (available at: www.pediatrics.org/cgi/content/full/118/3/1304). These topics are newborn screening as a public health system; factors contributing to the need for review of the newborn screening system; informed consent; tandem mass spectrometry; DNA analysis in newborn screening; status of newborn screening in the United States; and the effect of sample timing, preterm birth, diet, transfusion, and total parenteral nutrition on newborn screening results.
THE CONDENSATION OF CERTAIN γ-KETONIC ESTERS WITH AROMATIC ALDEHYDES. II (1933)

The condensation of benzaldehyde with methyl and ethyl α-aryl-β-benzoyl propionates in the presence of sodium methylate, followed by acidification, gave unsaturated ketonic acids. This result was unexpected in view of the previously described similar work in which lactols were formed; the only difference in the molecules is the absence of a substituent group in the benzoyl radical of the ester.The structure of the acids was carefully determined. On being heated they lost carbon dioxide, forming α, β-unsaturated ketones. One of the latter added hydrogen chloride to give two stereoisomeric saturated chloroketones, which were also synthesized by an independent method.
Analysis of Schottky Barrier Heights of Metal/SiC Contacts and Its Possible Application to High-Voltage Rectifying Devices (1997)

Schottky contacts of metal/3C-, 6H-, and 4H-SiC systems are investigated in this review. Most Schottky contacts having large barrier heights show good characteristics with low ideality factors. The barrier height depends on the metal work function without strong Fermi-level pinning for all polytypes, and linear relationships with slopes of about 0.2 to 0.7 are observed between the barrier height and the metal work function. Based on the analysis of metal/SiC systems, the fabrication of high-voltage rectifiers has been reported, and high voltages from 400 to 1100 V have been achieved using Pt/, Ti/, and Au/6H-SiC structures. In addition, high-temperature operation at 400 °C is performed for an Au/6H-SiC structure while supporting a high reverse bias (460 V). Using Ti/4H-SiC structures, high-voltage (≈︂1000 V) and low-power loss characteristics are realized, which is superior to Ti/6H-SiC Schottky rectifiers. To improve the reverse bias characteristics, an edge termination technique is employed for Ti/4H-SiC Schottky rectifiers, and the devices show excellent characteristics with a higher blocking voltage up to 1750 V compared with unterminated devices.
Prenatal fever and autism risk (2017)

Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.
A porin from Klebsiella pneumoniae: sequence homology, three-dimensional model, and complement binding (1995)

A recombinant plasmid containing ompK36, the gene coding for the Klebsiella pneumoniae outer membrane protein OmpK36, was constructed by transposon mutagenesis and subcloning. Clones were identified in a cosmid library in Escherichia coli on the basis of their reaction with antiserum against the OmpK36 protein and by the presence in gel electrophoretic analysis of a band in E. coli outer membranes migrating with a mobility corresponding to 36 kDa. The ompK36-encoded protein exhibited characteristic properties of porins, such as heat modifiability and resistance to trypsin. The sequence of the gene revealed that OmpK36 is a close relative of the enterobacterial porin family, with a high degree of homology with E. coli OmpC, PhoE, and OmpF. On the basis of the structures of OmpF and PhoE porins, determined previously by X-ray analysis, it appears likely that the three-dimensional structure of OmpK36 also contains the motif of a 16-stranded beta-barrel, with long loops on one end and short turns on the other. Like the OmpC porin from E. coli, OmpK36 contains a long insertion in loop 4. The results of a binding study of complement component C1q to OmpK36 and the analysis of the OmpK36 model suggest that C1q binding sites are covered by the lipopolysaccharide core in the native porin.
Alternative sources of reagents and supplies for fluorophore-assisted carbohydrate electrophoresis (FACE) (2002)

Ningguo Gao and Mark A. Lehrman Dept. Pharmacology UT-Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9041 # Contact information: (214)-648-2323; mark.lehrman@utsouthwestern.edu Fluorophore-assisted carbohydrate electrophoresis (FACE) is a simple, sensitive, and versatile method for analysis of both monosaccharides and oligosaccharides, and has become an important method in Glycobiology. Recently, the major provider of reagents and supplies for FACE has ceased production and shipping. To assist those who have relied upon the major provider for FACE reagents and supplies, the Editors have asked us to summarize alternative commercial sources and procedures that we have used (Gao and Lehrman, 2002a; Gao and Lehrman, 2002b). Our procedures are modified from those published previously (Jackson, P., 1994; Starr, C. M. et al., 1996).
Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. (1990)

Systemic infusion of low concentrations of tumor necrosis factor/cachectin (TNF) into mice that bear TNF-sensitive tumors leads to activation of coagulation, fibrin formation, and occlusive thrombosis exclusively within the tumor vascular bed. To identify mechanisms underlying the localization of this vascular procoagulant response, a tumor-derived polypeptide has been purified to homogeneity from supernatants of murine methylcholanthrene A-induced fibrosarcomas that induces endothelial tissue factor synthesis and expression (half-maximal response at approximately 300 pM), and augments the procoagulant response to TNF in a synergistic fashion. This tumor-derived polypeptide was identified as the murine homologue of vascular permeability factor (VPF) based on similar mobility on SDS-PAGE, an homologous NH2-terminal amino acid sequence, and recognition by a monospecific antibody to guinea pig VPF. In addition, VPF was shown to induce monocyte activation, as evidenced by expression of tissue factor. Finally, VPF was shown to induce monocyte chemotaxis across collagen membranes and endothelial cell monolayers. Taken together, these results indicate that VPF can modulate the coagulant properties of endothelium and monocytes, and can promote monocyte migration into the tumor bed. This suggests one mechanism through which tumor-derived mediators can alter properties of the vessel wall.
NEMO binding domain of IKK‐2 encompasses amino acids 735–745 (2006)

NF-kappaB activation is mediated by the IKK signalsome. Though this signalsome is comprised of IKK-1, IKK-2, and NEMO/IKKgamma, it is the interaction between IKK-2 and NEMO that is critical to formation of a functional signalsome. More specifically, previous reports have indicated that this interaction involves the C-terminal LDWSWL residues of IKK-2 (called the Nemo Binding Domain (NBD)) and the N-terminus of NEMO. In an effort to characterize the IKK-2:NEMO interaction, we have investigated several NBD-containing peptides for their ability to bind NEMO and inhibit the critical IKK-2:NEMO interaction. The six residue NBD peptide, LDWSWL, showed modest binding to NEMO and little inhibition of the IKK-2:NEMO interaction, whereas peptides containing the NBD plus additional flanking amino acids (NBD-containing peptides) more effectively bound NEMO and inhibited the interaction. These longer NBD-containing peptides may be required to give the NBD an appropriate conformation for recognition by NEMO and/or to provide for additional interactions with NEMO.
Origin of the collapse of tunnel magnetoresistance at high annealing temperature in CoFeB/MgO perpendicular magnetic tunnel junctions (2011)

We have investigated a tunnel magnetoresistance (TMR) ratio of CoFeB/MgO perpendicular magnetic tunnel junctions (p-MTJs) with a 40 nm diameter as a function of an annealing temperature Ta. The TMR ratio at room temperature (RT) increases with increasing Ta and reaches 149% at Ta = 350 °C, and further increase of Ta results in a strong reduction of the TMR ratio, i.e., 2% at Ta = 400 °C. The temperature dependence of the junction resistance versus magnetic field loops reveals that the reduced TMR ratio at RT is due to the disappearance of a stable antiparallel magnetization configuration. We find that reduction of dipole coupling restores the TMR ratio.
Synthesis and Single-Crystal X-ray Structure of a Highly Symmetrical C 60 Derivative, C 60 Br 24 (1992)

C(60) and liquid bromine react to form C(60)Br(24), a crystalline compound isolated as a bromine solvate, C(60)Br(24)(Br(2))(x), The x-ray crystal structure defines a new pattern of addition to the carbon skeleton that imparts a rare high symmetry. The parent C(60) framework is recognizable in C(60)Br(24), but sp(3) carbons at sites of bromination distort the surface, affecting conformations of all of the hexagonal and pentagonal rings. Twenty-four bromine atoms envelop the carbon core, shielding the 18 remaining double bonds from addition. At 150 degrees to 200 degrees C there is effectively quantitative reversion of C(60)Br(24) to C(60) and Br(2).
Plasma power can make better powders (2004)

It may be a truism to say that round powders pack better, but spheroidisation of powder particles is one of the successful commercial applications of induction plasma technology and can play a key role in substantial improvement of powder quality and fluidity…
Structure-activity relationships of isothiocyanates as mechanism-based inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. (1994)

A structure-activity relationship study was carried out to identify structural features in arylalkyl and alkyl isothiocyanates that are associated with the inhibitory potency of these compounds against lung tumorigenesis induced in A/J mice by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These features include the alkyl chain length, phenyl substitution, and secondary isothiocyanates. The naturally occurring allyl isothiocyanate, phenethyl isothiocyanate, and the synthetic analogues such as 6-phenylhexyl isothiocyanate, 8-phenyloctyl isothiocyanate, 10-phenyldecyl isothiocyanate, 1,2-diphenylethyl isothiocyanate, 2,2-diphenylethyl isothiocyanate, and alkyl isothiocyanates (with 1-hexyl, 2-hexyl, and 1-dodecyl as alkyl moieties) were assayed in mice for their tumor inhibitory potential. The isothiocyanates were given in corn oil by gavage at doses of either 0.04, 0.1, and 0.2 mumol or 1 and 5 mumol 2 h prior to a single i.p. injection of 10 mumol NNK. Mice were sacrificed 16 weeks later and lung adenomas were counted. At 0.2 mumol, 8-phenyloctyl isothiocyanate and 10-phenyldecyl isothiocyanate were stronger inhibitors than the previously tested 6-phenylhexyl isothiocyanate, but the difference in potency was not obvious at the lower doses. At both 1 and 5 mumol, allyl isothiocyanate was inactive, while the other five synthetic isothiocyanates were considerably more potent than phenethyl isothiocyanate. In the alkyl isothiocyanate series, 2-hexyl isothiocyanate was more potent than 1-hexyl isothiocyanate, while 1-dodecyl isothiocyanate was the most potent at 1 mumol, reducing tumor multiplicity in the group treated with NNK alone from 11.1 to the background level. Also, 1,2-diphenylethyl isothiocyanate appeared to be a stronger inhibitor than 2,2-diphenylethyl isothiocyanate. In this study we have shown that the phenyl moiety is not essential for the inhibitory activity since alkyl isothiocyanates exhibit strong inhibitory effects against lung tumorigenesis. We have also shown that secondary isothiocyanates possess a higher potency than their structural isomers bearing a primary isothiocyanate. From results of this study and of seven previously studied isothiocyanates, we conclude that the observed inhibitory potency of isothiocyanates in the A/J mouse lung tumor model is correlated with their partition coefficients (log P) and the pseudo first order rate constants for the reaction of isothiocyanates toward glutathione (kobs). These results reveal that both high lipophilicity and low reactivity of isothiocyanates are important for inhibitory activity toward NNK-induced lung tumorigenesis. These observations provide a structural basis for the discovery of more effective chemopreventive agents.
Gene Expression Profiling Reveals Reproducible Human Lung Adenocarcinoma Subtypes in Multiple Independent Patient Cohorts (2006)

DNA microarray analysis of lung adenocarcinomas identified reproducible tumor subtypes which differ significantly in clinically important behaviors such as stage-specific survival.
Titanium and Zirconium in Organic Synthesis (2002)

Foreword.Preface.List of Contributors.Synthesis and Reactivity of Zirconocene Derivatives (E. Negishi & S. Huo). Zirconacyclopentadienes in Organic Synthesis (T. Takahashi & Y. Li). Elaboration of Organozirconium Species by Insertion of Carbenoids (S. Dixon & R. J. Whitby). Hydrozirconation and Further Transmetalation Reactions (B. H. Lipshutz, S. S. Pfeiffer, K. Noson & T. Tomioka). Acylzirconocenes in Organic Synthesis (Y. Hanzawa). Chiral Zirconium Catalysts for Enantioselective Synthesis (A. H. Hoveyda). gem Metallozirconocenes in Organic Synthesis (V. M. Dembitsky & M. Srebnik). Cationic Zirconocene Species in Organic Synthesis (K. Suzuki, L. Hintermann & S. Yamanoi). Titanium (II) Alkoxides in Organic Synthesis (F. Sato & H. Urabe). Organometallic Chemistry of Titanocene and Zirconocene Complexes with Bis(trimethylsilyl)acetylene as the Basis for Applications in Organic Synthesis (U. Rosenthal & V. V. Burlakov). Titanium Mediated Synthesis of Cyclopropanols and Cyclopropylamines (A. de Meijere, S. I. Kozhushkov & A. I. Savchenko). Titanocene Catalyzed Epoxide Opening (A. Gansauer & B. Rinker). Synthesis and Reactivity of Allyltitanium Derivatives (J. Szymoniak & C. Moise). Titanium based Olefin Metathesis and Related Reactions (T. Takeda).Index.