gebhart/patrepeval huggingface dataset:
High-Resolution Conformation of Gramicidin A in a Lipid Bilayer by Solid-State NMR (1993)

Solid-state nuclear magnetic resonance spectroscopy of uniformly aligned preparations of gramicidin A in lipid bilayers has been used to elucidate a high-resolution dimeric structure of the cation channel conformation solely on the basis of the amino acid sequence and 144 orientational constraints. This initial structure defines the helical pitch as single-stranded, fixes the number of residues per turn at six to seven, specifies the helix sense as right-handed, and identifies the hydrogen bonds. Refinement of this initial structure yields reasonable hydrogen-bonding distances with only minimal changes in the torsion angles.
Effects of PPARγ ligand rosiglitazone on AGS gastric cancer cells growth (2009)

Objective To investigated the effects of PPARγ ligand rosiglitazone on cell viability and apeptosis in AGS gastric cancer cell line and determine the possible mechanisms of rosiglitazone.Methods MTS method was used to measure the cell viability,flow cytometry analysis Was used to measure apoptosis.The PPARγ,HCaRG,DLK1 mRNA and protein was examined by real-time PCR and westem blot.Results The cell viability of AGS cells treated with rosiglitazone was decreased in concentration-and time-dependent manner.Preincabation with irreversible PPARγ antagonist GW9662 partly revePged the decrease of the cell viability induced by rosiglitazone.After treating apoptosis in AGS cells induced by different concentration rosiglitazone,the percentage of apoptosis was higher than those in control group.Preincubation with GW9662 cannot reverse the increase of the cell apoptosis induced by rosiglitazone.Rosiglitazone markedly induced the expression of PPARγ,HCaRG,and DLK1 in AGS cell line.Pre-treatment with GW9662 markedly reduced rosiglitazone-induced PPAγand DLK1 expression,but could not block HCaRG expression,Conclusion Rosiglitazone suppressed AGS cells growth via PPARγ-dependent and-independent pathway. Upregulation of HCaRG and DLK1 may be one of the mechanisms underlying the anticancer effect of rosigltizaone in gastric cancer.

Key words: 
Thiazolidinediones/PD; Stomach neoplasms/DT; Cell proliferation; Apoptosis; PPAR gamma/ME; Gene expression
Three polymorphs (α, β, and δ) ofD-mannitol at 100 K (2003)

In the monoclinic delta polymorph of D-mannitol, C(6)H(14)O(6), both the molecule and the packing have approximate twofold rotational symmetry. The P2(1) structure thus approximates space group C222(1), and the alpha' polymorph, previously reported in that space group, is almost certainly identical to the delta polymorph. However, torsion angles along the main backbone of the molecule deviate from twofold symmetry by as much as 7.4 (3) degrees and the hydrogen-bonding pattern does not conform to the higher symmetry. The alpha polymorph reported here is identical to the previously reported kappa polymorph, and the low-temperature structure of the beta polymorph agrees well with previously reported room-temperature determinations. The range of C-O bond lengths over the three polymorphs is 1.428 (2)-1.437 (4) A, and the range of C-C distances is 1.515 (4)-1.5406 (19) A. The delta polymorph has the highest density of the three, both at room temperature and at 100 K.
A Common Language for Physical Mapping of the Human Genome (1989)

In a report issued in January 1988, the National Research&#13;\nCouncil (NRC) Committee on the Mapping and Sequencing&#13;\nof the Human Genome, on which the present authors&#13;\nserved, recommended a staged mapping and sequencing project&#13;\nwith early emphases on physical mapping of human DNA, mapping and sequencing of the genomes of model organisms, and the development of sequencing technology (1). As the Committee's recommendations on physical mapping are beginning to be implemented on a substantial scale, it is timely to review these recommendations in the light of recent technical advances. In particular, the polymerase chain reaction (PCR) (2), a method that has only come&#13;\ninto widespread use during the past 2 years, seems to us to offer a path toward a physical map that largely circumvents two problems that were prominent in the NRC Committee's discussions. One of these was the difficulty of merging mapping data gathered by diverse methods in different laboratories into a consensus physical map. The second was the logistics and expense of managing the huge collections&#13;\nof cloned segments on which the mapping data would depend&#13;\nalmost absolutely.
Acute Intraoperative Endotracheal Tube Obstruction Associated with a Heat and Moisture Exchanger in an Infant (1997)

To the Editor: We report a small infant who developed acute airway obstruction under general anesthesia after a heat and moisture exchanger (HME) was added to the anesthesia circuit to preserve heat and humidity. The use of this device is not free of complications. This 6-wk-old, 3-kg former premature male infant was scheduled for herniorrhaphy and orchiopexy. After an uneventful induction, the trachea was intubated, and 2.0 mL of 0.25% bupivacaine was injected into the caudal space. General anesthesia was maintained with oxygen, nitrous oxide, isoflurane, and pancuronium. The patient's lungs were mechanically ventilated, and breath sounds were equal bilaterally. Peak inspiratory pressure was 24 cm H2 O. A neonatal and infant HME (Gibeck, Upplands Vasby, Sweden) was placed between the 3.0 endotracheal tube (ETT) and the breathing circuit of the circle system. Within the next minute, the SpO2 decreased rapidly from 100% to 60%. Manual ventilation was initiated, and the SpO2 increased to 100% in less than 60 s. Breath sounds were equal bilaterally, the ETT was suctioned, and no secretions were noted. CO2 was detected by capnography. On inspection, a 2 x 3 mm piece of paper was noted to be swirling between the 15-mm connector of the ETT and the HME. The HME was removed and inspected, and it appeared intact (Figure 1). The patient's lungs were mechanically ventilated, and the peak inspiratory pressure returned to baseline. The use of the HME was abandoned. No further episode of peripheral oxygen desaturation was noted. The surgical procedure was completed, and the patient was extubated without complications.Figure 1: The small piece of paper (arrow) that caused airway obstruction is shown. The heat and moisture exchanger (a) is disconnected from the endotracheal tube (b).Defects in the HME (i.e., dislodgement of its components) have been associated with the inability to adequately ventilate the lungs [1-3]. The use of the HME in patients with active bleeding from the ETT or with an active, heated, humidified circuit has been associated with airway obstruction and should be avoided [3-5]. When using a HME in the breathing circuit, the HME should be placed in the circuit and the circuit tested and inspected before beginning anesthesia. Alfonso Casta, MD Constance S. Houck, MD Department of Anesthesia; Children's Hospital; Boston, MA 02115
Polymeric Drug Delivery Systems (1993)

Although already in 1971 Yolles et al. discussed the design of polymeric devices for the delivery of drugs (1) and a patent was filed by Boswell and Scribner on the use of polylactic acid in drug delivery systems (2), two widely cited papers by Yolles et al. from the year 1973 (3,4) are often regarded as the starting point of the development of polymeric drug delivery systems. From the modest beginnings in 1973 when drugs were simply mixed into a polymeric matrix, an avalanche of theoretical and practical advances led to the rapid development of a large number of distinct system configurations and device designs. Today, drug delivery devices can be conveniently divided into two large categories relating to "controlled drug release systems" and "targeted drug delivery systems." The definition of controlled release versus targeted drug delivery is based on the relationship between the site of drug release and the
Construction of Catalase DeficientEscherichia coliStrains for the Production of Uricase (1996)

To produce catalase-free uricase preparations, we constructed catalase-deficient strains from Escherichai coli MC1000 and MM294 and used them as recombinant host strains. The parent strains and catalase-deficient strains showed no differences in the growth characteristics by shaking culture in Erlenmeyer flasks. The catalase deficient strain derived from MC1000 transformed with the uricase expression plasmid pUT118 (strain SN0037) had growth characteristics and the uricase productivity comparable to those of the parent host strain MC1000 in fed-batch culture in a jar fermentor and no catalase activity was detected in cell-free extracts. However, the katG disrupted strains from MM294 carrying pUT118 had poor growth and their uricase productivities were low compared to those of the parent strain MM294. Using the strain SN0037, a catalase-free uricase preparation was obtained with fewer purification procedures and the final recovery of uricase activity was improved. The catalase-deficient E. coli host strain will be a suitable host for the production of the uricase, free of catalase activity, in high yield.
Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation (2001)

The Notch gene family encodes large transmembrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. To assess the in vivo role of the Notch2 gene, we constructed a targeted mutation, Notch2(del1). Unexpectedly, we found that alternative splicing of the Notch2(del1) mutant allele leads to the production of two different in-frame transcripts that delete either one or two EGF repeats of the Notch2 protein, suggesting that this allele is a hypomorphic Notch2 mutation. Mice homozygous for the Notch2(del1) mutation died perinatally from defects in glomerular development in the kidney. Notch2(del1)/Notch2(del1 )mutant kidneys were hypoplastic and mutant glomeruli lacked a normal capillary tuft. The Notch ligand encoded by the Jag1 gene was expressed in developing glomeruli in cells adjacent to Notch2-expressing cells. We show that mice heterozygous for both the Notch2(del1) and Jag1(dDSL) mutations exhibit a glomerular defect similar to, but less severe than, that of Notch2(del1)/Notch2(del1 )homozygotes. The co-localization and genetic interaction of Jag1 and Notch2 imply that this ligand and receptor physically interact, forming part of the signal transduction pathway required for glomerular differentiation and patterning. Notch2(del1)/Notch2(del1 )homozygotes also display myocardial hypoplasia, edema and hyperplasia of cells associated with the hyaloid vasculature of the eye. These data identify novel developmental roles for Notch2 in kidney, heart and eye development.
Hedgehog signaling correlates with hepatocellular carcinoma progression (2005)

9610 Background: Hedgehog (Hh) pathway activation promotes foregut tumors, such as pancreatic cancer. Whether Hh activity modulates hepatocellular carcinoma (HCC) pathogenesis is unknown. Although mature hepatocytes do not express the pathway, liver development requires Hh signaling. Blocking Hh prevents hepatogenesis and promotes pancreatic differentiation, suggesting a common precursor for liver and pancreas. The Hh pathway is activated when Sonic (Shh) or Indian (Ihh) ligands bind to the receptor, Patched (Ptc). When unoccupied by ligand, Ptc is a tumor suppressor because it binds Smoothened (Smo), an oncogenic protein, preventing Smo from activating Gli1. When ligand binds to Ptc, Smo is released and activates Gli1, which induces the transcription of its target gene, Ptc. Thus, Ptc mRNA levels increase with Hh activity. Aim: Determine if mRNAs of tumor suppressor (Ptc) or oncogenic (Shh, Ihh, Smo, Gli1) Hh pathway components are altered in human HCC. Methods: Total RNA was extracted from HCC and non-cancerous livers of 12 adults with HCC and various chronic liver diseases (alcoholic 8%, viral 50%, cryptogenic cirrhosis 25%). Two-step real-time PCR was done to compare expression of Shh, Ihh, Ptc, Smo, and Gli1 in HCC and non-tumor tissue from each patient. *p<0.05. Results: HCC ranged from 1–11 cm (mean 4±3 cm). The oncogenic factor, Smo, averaged >2-fold increase in the HCCs compared to non-tumorous liver. Regression analysis demonstrated that Smo mRNA levels correlated with HCC size*. In 8/12 (67%) HCCs, expression of the tumor suppressor, Ptc, was also significantly different than that of non-cancerous liver: 6 HCC had a 3× decrease, while 2 had an 11× increase in Ptc mRNA. Tumors with decreased Ptc were larger than HCC with normal expression (5±4 v. 3±1 cm)*. Serum levels of α-fetoprotein were barely elevated in any patient (mean 6.4±4.3 ng/mL) and did not correlate with HCC size or expression of Hh signaling components. Conclusion: Human HCCs have altered expression of Hh pathway components that regulate development of the liver from endodermal precursors. Although this pathway has been implicated in carcinogenesis of other endodermally-derived tissues, this is the first evidence for altered Hh pathway activity in hepatocarcinogenesis. No significant financial relationships to disclose.
6-(Substituted methylene)penems, potent broad spectrum inhibitors of bacterial .BETA.-lactamase. III. Structure-activity relationships of the 5-membered heterocyclic derivatives. (1991)

Sodium (5RS)-Z-6-(heterocyclylmethylene)penem-3-carboxylates (2) are a series of extremely potent inhibitors of bacterial beta-lactamases. A variety of 5-membered heteroaromatic derivatives have been prepared and structure-activity studies reveal a preferred substituent orientation. One of these derivatives, the 1-methyl-1,2,3-triazolyl compound (5m) is a more potent synergist of amoxycillin than clavulanic acid, sulbactam or tazobactam.
Resonant Field Enhancements from Metal Nanoparticle Arrays (2003)

Theoretical and semiempirical studies of two-dimensional (2D) metal nanoparticle arrays under periodic boundary conditions yield quantitative estimates of their electromagnetic (EM) field factors, revealing a critical relationship between particle size and interparticle spacing. A new theory based on the RLC circuit analogy has been developed to produce analytical values for EM field enhancements within the arrays. Numerical and analytical calculations suggest that the average EM enhancements for Raman scattering (Ḡ) can approach 2 × 1011 for Ag nanodisks (5 × 1010 for Au) and 2 × 109 for Ag nanosphere arrays (5 × 108 for Au). Radiative losses related to retardation or damping effects are less critical to the EM field enhancements from periodic arrays compared to that from other nanostructured metal substrates. These findings suggest a straightforward approach for engineering nanostructured arrays with direct application toward surface-enhanced Raman scattering (SERS).
Humanization of a mouse anti-human IgE antibody: a potential therapeutic for IgE-mediated allergies (1993)

Mouse mAb TES-C21(C21) recognizes an epitope on human IgE and, therefore, has potential as a therapeutic agent in patients with IgE-mediated allergies such as hay fever, food and drug allergies and extrinsic asthma. The clinical usefulness of mouse antibodies is limited, however, due to their immunogenicity in humans. Mouse C21 antibody was humanized by complementarity determining region (CDR) grafting with the aim of developing an effective and safe therapeutic for the treatment of IgE-mediated allergies. The CDR-grafted, or reshaped human, C21 variable regions were carefully designed using a specially constructed molecular model of the mouse C21 variable regions. A key step in the design of reshaped human variable regions is the selection of the human framework regions (FRs) to serve as the backbones of the reshaped human variable regions. Two approaches to the selection of human FRs were tested: (i) selection from human consensus sequences and (ii) selection from individual human antibodies. The reshaped human and mouse C21 antibodies were tested and compared using a biosensor to measure the kinetics of binding to human IgE. Surprisingly, a few of the reshaped human C21 antibodies exhibited patterns of binding and affinities that were essentially identical to those of mouse C21 antibody.
Childhood predictors of adult obesity: a systematic review. (1999)

Risk factors for obesity included parental fatness, social factors, birth weight, timing or rate of maturation, physical activity, dietary factors and other behavioural or psychological factors. Offspring of obese parent(s) were consistently seen to be at increased risk of fatness, although few studies have looked at this relationship over longer periods of childhood and into adulthood. The relative contributions of genes and inherited lifestyle factors to the parent-child fatness association remain largely unknown. No clear relationship is reported between socio-economic status (SES) in early life and childhood fatness. However, a strong consistent relationship is observed between low SES in early life and increased fatness in adulthood. Studies investigating SES were generally large but very few considered confounding by parental fatness. Women who change social class (social mobility) show the prevalence of obesity of the class they join, an association which is not present in men. The influence of other social factors such as family size, number of parents at home and childcare have been little researched. There is good evidence from large and reasonably long-term studies for an apparently clear relationship for increased fatness with higher birth weight, but in studies which attempted to address potential confounding by gestational age, parental fatness, or social group, the relationship was less consistent. The relationship between earlier maturation and greater subsequent fatness was investigated in predominantly smaller, but also a few large studies. Again, this relationship appeared to be consistent, but in general, the studies had not investigated whether there was confounding by other factors, including parental fatness, SES, earlier fatness in childhood, or dietary or activity behaviours. Studies investigating the role of diet or activity were generally small, and included diverse methods of risk factor measurement. There was almost no evidence for an influence of activity in infancy on later fatness, and inconsistent but suggestive evidence for a protective effect of activity in childhood on later fatness. No clear evidence for an effect of infant feeding on later fatness emerged, but follow-up to adulthood was rare, with only one study measuring fatness after 7y. Studies investigating diet in childhood were limited and inconc
Human immunodeficiency virus pseudotypes with expanded cellular and species tropism (1990)

One mechanism for expanding the cellular tropism of a virus is through the formation of phenotypically mixed particles or pseudotypes, a process commonly occurring during viral assembly in cells infected with two or more viruses. We report here that dual infection of cells with human immunodeficiency virus (HIV) and a murine amphotropic retrovirus leads to the production of HIV pseudotypes that have acquired the host range of the amphotropic retrovirus and are capable of infecting not only CD4- human cells but also mouse cells. The replication of the HIV pseudotypes in the various CD4- cells was determined by measuring the appearance of HIV antigens in the supernatants, by cocultivation of CD4+ CEM cells with the infected CD4- cells, and in some cases by assaying the culture supernatants directly for infectious virus. Of the cells tested, human foreskin fibroblasts were the best host cells, and by in situ cytohybridization, we were able to document that all cells in the culture were infected. In addition, the temporal appearance of HIV-specific proteins in the HIV pseudotype-infected fibroblasts was similar to that seen in CD4+ CEM cells. If the human fibroblasts were first infected with the amphotropic retrovirus, they demonstrated the property of superinfection exclusion and were resistant to subsequent infection by the HIV pseudotype. In other cell lines, including the human glioblastoma-derived cell line U373MG, HeLa cells, BALB/c mouse embryo cells, and SC-1 wild mouse cells, although the HIV pseudotype infection appeared to be less efficient, substantial amounts of HIV were nevertheless produced. These results indicate that the HIV (amphotropic retrovirus) pseudotypes may be useful for studying the molecular biology of HIV infections in a wide range of cells.
Metallocene-Based Branch−Block Thermoplastic Elastomers (2000)

Long chain branched (LCB) polyethylene block copolymers having thermoplastic elastomer character were made using mixed metallocene catalysts. Conceptually, the synthesis can be divided into two steps. Step 1 involves the generation of vinyl-terminated, crystallizable macromonomers, and step 2 involves the incorporation of these macromonomers into an amorphous or plastomeric copolymer backbone. In practice, the two steps may be conducted sequentially or simultaneously. The polymer properties depend on the catalyst pair and the process conditions selected, which determine the populations of reactive macromonomer and the probability of incorporating them into the backbone. One such useful pair is the mixture of Cp2ZrCl2 and (C5Me4SiMe2NC12H23)TiCl2, activated with MAO. In the presence of a mixed ethylene/butene feed the Cp2ZrCl2 catalyst, by virtue of its low comonomer incorporating capability, will produce primarily crystalline polyethylene macromonomers. The titanium catalyst, on the other hand, has a higher affinity for comonomers and will consume comonomer and macromonomers during the polymerization which produces plastomeric backbone containing, in one case, over 20 mol % butene. Microtensile test on the polymers showed good elastic recovery and good high-temperature tensile strength. The properties of the resultant comblike polymers will be governed by the topological details of the branched polymer as well as the LCB distribution. To study the latter distribution, branched model polymers having dissimilar LCB and backbone compositions were synthesized. GPC-FTIR analysis provided the LCB distribution pattern, revealing a progression of statistically branched polymers with the highest molecular weight molecules containing the highest levels of branching. Upon cooling from the melt, the crystalline segments (primarily in the LCB portions) would cocrystallize to form crystalline domains embedded in an amorphous matrix, as confirmed by transmission electron microscopy.
Synthesis and evaluation of novel spermidine derivatives as targeted cancer chemotherapeutic agents (1992)

The utility of the spermidine moiety as the homing device for the selective delivery of chemotherapeutic and diagnostic agents into cancer cells was explored. Two spermidine analogs containing a cytotoxic agent were synthesized, N-[3,4-bis(benzyloxy)phenethyl]-N alpha-(3-amino-propyl)-L-ornithinamide trihydrochloride, 1a and N-[4-]bis(2-chloroethyl)amino]phenethyl]-N alpha-(3-aminopropyl)-L- ornithinamide tetrahydrochloride, 1b. These compounds were prepared from the fully protected spermidine molecule with a carboxyl group side chain, 8. The ability of the polyamine cytotoxic agents to inhibit B16-BL6 melanoma cell growth in culture was examined. The effects of pretreatment with DFMO on the activity of the synthesized compounds was also studied. The IC50 values of compounds 1a and 1b were on the same order of magnitude as the control compounds, N-acetyldopamine and chlorambucil, respectively. The inhibitory activities of compounds 1a and 1b were not enhanced by pretreatment with DFMO, suggesting that depletion of intracellular polyamines did not enhance the activity of these compounds.
Carbenes in Constrained Systems I: 1,3 CH, Insertion Reaction of Adamantylidene within the β‐Cyclodextrin Cavity (1993)

The first intra- and intermolecular carbene insertions within any constrained molecular reaction vessel was detected in the photolysis of the solid inclusion complex 1·β-cyclodextrin(CD). NMR and/or FAB mass spectra reveal the formation of products such as 2·β-CD and 3·β-CD.