gebhart/patrepeval huggingface dataset:
Inducing Single-Molecule Magnetism in a Family of Loop-of-Loops Aggregates: Heterometallic Mn40Na4 Clusters and the Homometallic Mn44 Analogue (2010)

The syntheses, crystal structures, and magnetic properties of a new family of heterometallic Mn(40)Na(4) and homometallic Mn(44) loop-of-loops aggregates are reported. The reactions of [Mn(3)O(O(2)CMe)(6)(py)(3)]·py with 1,3-propanediol (pdH(2)) and 2-methyl-1,3-propanediol (mpdH(2)) in the presence of NaN(3) afforded [Mn(10)Na(μ(3)-O)(2)(O(2)CMe)(13)(pd)(6)(py)(2)](4) (1)(4) and [Mn(10)Na(μ(3)-O)(2)(O(2)CMe)(13)(mpd)(6)(py)(H(2)O)](4) (2)(4), respectively. Mn(40)Na(4) complexes (1)(4) and (2)(4) consist of four Mn(10) loops linked through Na(+) ions to give a supramolecular aggregate with a saddle-like topology. Magnetic characterization of compound (1)(4) showed that each Mn(10) loop has an S = 4 ground-state spin and displays frequency-dependent in-phase and out-of-phase ac susceptibility signals. It also exhibits hysteresis loops that, however, are not typical of single-molecule magnets (SMMs) due to the existence of interloop interactions between the neighboring Mn(10) units of (1)(4) through the diamagnetic Na(+) ions, and also intermolecular interactions between different Mn(40)Na(4) aggregates. The magnetically discrete Mn(44) analogue was targeted with high priority and finally prepared from the reaction of [Mn(3)O(O(2)CMe)(6)(py)(3)]·py with pdH(2) in the presence of Mn(ClO(4))(2)·6H(2)O. The loop-of-loops structure of [Mn(44)(μ(3)-O)(8)(O(2)CMe)(52)(pd)(24)(py)(8)](ClO(4))(OH)(3) (3) is essentially identical to those of (1)(4) and (2)(4), with the most significant difference being that the four Na(+) ions of (1)(4) and (2)(4) have been replaced with Mn(2+) ions. Compound 3 is thus best described magnetically as a Mn(44) cluster. In accord with this description and the stronger exchange coupling between the four Mn(10) loops expected through the connecting Mn(2+) ions, magnetic susceptibility measurements revealed that 3 has an S = 6 ground-state spin and displays frequency-dependent in-phase and out-of-phase ac signals. Magnetization vs dc field sweeps on single-crystals of 3 displayed scan rate- and temperature-dependent hysteresis loops confirming that complex 3 is a new SMM, and is thus the second largest Mn cluster and SMM reported to date.
Cucurbitane Glycosides from Unripe Fruits of Lo Han Kuo (<i>Siraitia grosvenori</i>) (2006)

From the unripe fruits of Lo Han Kuo (Siraitia grosvenori), a Chinese medicinal plant, two new cucurbitane triterpene glycosides, 20-hydroxy-11-oxomogroside IA(1) (1) and 11-oxomogroside IIE (2), were isolated along with five known cucurbitane glycosides, 11-oxomogroside IA(1) (3), mogroside IIE (4), mogroside III (5), mogroside IVA (6), and mogroside V (7), and two flavonoid glycosides, kaempferol 7-O-alpha-L-rhamnopyranoside (8) and kaempferol 3,7-di-O-alpha-L-rhamnopyranoside (9). Their structures were determined on the basis of detailed analyses of 1D, 2D-NMR spectroscopic methods and by comparing with literature values. This paper describes the first investigation of unripe bitter Lo Han Kuo fruits.
Metastatic signature in lung cancer is associated with sensitivity to anti‐integrin αV monoclonal antibody intetumumab (2014)

Intetumumab is a fully human monoclonal antibody that inhibits αv integrins. It has been shown in in vitro assays to effectively inhibit cell viability, metastasis, and adhesion of human cancer cells and endothelial cells. However, the response to Intetumumab varies in different tumor cell lines. To understand the growth inhibition mechanism of Intetumumab and to identify a molecular signature that can predict sensitivity, we focused on lung cancer cell lines and performed a series of proliferation assays. We then assessed the global gene expression profiles, DNA copy number variations, and microRNA profiles from a total of 23 lung cancer lines. The results revealed that lung cancer sensitivity to Intetumumab is associated with several chromosomal alterations, particularly genetic loss at chromosome arm 19p, which resulted in gene expression changes. We identified a genetic signature that can be used to predict Intetumumab sensitivity for lung cancer cell lines. Independently, microRNA analysis revealed a panel of signature microRNAs that includes several markers of epithelial to mesenchymal transition and tumor metastasis such as miR-200 family and miR-205. Both the genetic and microRNA signatures provide insights into the potential mechanism of Intetumumab activity and serve as the first step to develop a patient stratification strategy for Intetumumab therapy in lung cancer.
Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy (2002)

Protein conformational disorders (PCDs), such as Alzheimer's disease, Huntington's disease (HD), Parkinson's disease and oculopharyngeal muscular dystrophy, are associated with proteins that misfold and aggregate. Here we have used exon 1 of the HD gene with expanded polyglutamine [poly(Q)] repeats and enhanced green fluorescent protein tagged to 19 alanines as models for aggregate-prone proteins, to investigate the pathways mediating their degradation. Autophagy is involved in the degradation of these model proteins, since they accumulated when cells were treated with different inhibitors acting at distinct stages of the autophagy-lysosome pathway, in two different cell lines. Furthermore, rapamycin, which stimulates autophagy, enhanced the clearance of our aggregate-prone proteins. Rapamycin also reduced the appearance of aggregates and the cell death associated with the poly(Q) and polyalanine [poly(A)] expansions. Since rapamycin is used clinically, this drug or related analogues may be suitable candidates for therapeutic investigation in HD and related diseases. We have also re-examined the role of the proteasome, since previous studies in poly(Q) diseases have used lactacystin as an inhibitor--recent studies have shown that lactacystin may also affect lysosomal function. Both lactacystin and the specific proteasomal inhibitor epoxomicin increased soluble protein levels of the poly(Q) constructs, suggesting that these are also cleared by the proteasome. However, while poly(Q) aggregation was enhanced by lactacystin in our inducible PC12 cell model, aggregation was reduced by epoxomicin, suggesting that some other protein(s) induced by epoxomicin may regulate poly(Q) aggregation.
Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages (2008)

M-CSF/CSF-1 supports the proliferation and differentiation of monocytes and macrophages. In mice, CSF-1 also promotes proinflammatory responses in vivo by regulating mature macrophage functions, but little is known about the acute effects of this growth factor on mature human macrophages. Here, we show that in contrast to its effects on mouse bone marrow-derived macrophages, CSF-1 did not induce expression of urokinase plasminogen activator mRNA, repress expression of apolipoprotein E mRNA, or prime LPS-induced TNF and IL-6 secretion in human monocyte-derived macrophages (HMDM) from several independent donors. Instead, we show by expression profiling that CSF-1 modulates the HMDM transcriptome to favor a proatherogenic environment. CSF-1 induced expression of the proatherogenic chemokines CXCL10/IFN-inducible protein 10, CCL2, and CCL7 but repressed expression of the antiatherogenic chemokine receptor CXCR4. CSF-1 also up-regulated genes encoding enzymes of the cholesterol biosynthetic pathway (HMGCR, MVD, IDI1, FDPS, SQLE, CYP51A1, EBP, NSDHL, DHCR7, and DHCR24), and expression of ABCG1, encoding a cholesterol efflux transporter, was repressed. Consistent with these effects, CSF-1 increased levels of free cholesterol in HMDM, and the selective CSF-1R kinase inhibitor GW2580 ablated this response. These data demonstrate that CSF-1 represents a further link between inflammation and cardiovascular disease and suggest two distinct mechanisms by which CSF-1, which is known to be present in atherosclerotic lesions, may contribute to plaque progression.
The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3 (1998)

We cloned the mouse homologue of the chemokine receptor CXCR3, which is located in mouse chromosome X. We screened a large panel of chemokines for their ability to induce a calcium flux in mouse CXCR3-transfected cells and identified a new ligand for this receptor, the recently reported CC chemokine 6Ckine. This represents an example of a CC chemokine, which binds to a CXC chemokine receptor. Like other ligands of this receptor, 6Ckine has angiostatic properties. 6Ckine is known to chemoattract T cells. In line with this, CXCR3 is expressed preferentially in Th1 cells and in lymphoid organs of the IL-10(-/-) mouse that develops chronic colitis. Its ability to attract T cells as well as its angiostatic properties suggest that 6Ckine may be an effective anti-tumor agent.
El recurso de casación en materia tributaria: a propósito de su reciente reforma (2011)

Materials assembled by coordination interactions between naturally abundant polyphenols and metals are of interest for a wide range of applications, including crystallization, catalysis, and drug delivery. Such an interest has led to the development of thin films with tunable, dynamic properties, however, creating bulk materials remains a challenge. Reported here is a class of metallogels formed by direct gelation between inexpensive, naturally abundant tannic acid and group(IV) metal ions. The metallogels exhibit diverse properties, including self-healing and transparency, and can be doped with various materials by in situ co-gelation. The robustness and flexibility, combined with the ease, low cost, and scalability of the coordination-driven assembly process make these metallogels potential candidates for chemical, biomedical, and environmental applications.
Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival (2004)

Hematopoietic stem cells (HSCs) sustain blood formation throughout life. Pathways regulating maintenance of adult HSCs are largely unknown. Here we report that the Ets-related transcription factor Tel/Etv6, the product of a locus frequently involved in translocations in leukemia, is a selective regulator of HSC survival. Following inactivation of Tel/Etv6, HSCs are lost in the adult bone marrow but their progeny are unaffected and transiently sustain blood formation. Accordingly, absence of Tel/Etv6 after lineage commitment is ostensibly without consequence except for unexpected impairment of maturation of megakaryocytes. Thus, we establish Tel/Etv6 as a selective and essential regulator of postembryonic HSCs.
Cellular Internalization of Oligodeoxynucleotides (1994)

Although the addition of oligodeoxynucleotides to cell cultures has been demonstrated to effectively inhibit intracellular gene expression, such findings have been in contrast to the prevailing view that cells are impermeable to negatively charged large molecules. With this in mind, several groups have attempted to modify oligos in order to circumvent the problem of negative charge. Thus, methylphosphonates are ionically neutral, and poly-L-lysine has been linked to oligos to supply a strong positive charge. Others have made various oligonucleotide-protein conjugates to aid internalization, while the benefits of oligo encapsulation into liposomes have also been explored. During the last several years, it has become clear that even highly negatively charged oligonucleotides (i.e., phosphodiesters and phosphorothioates) are actively internalized by cells in culture. Furthermore, it has become equally apparent that backbone or pendant oligonucleotide modifications can alter olionucleotide uptake characteristics, although not always in the way intended. In this chapter, we will review the current state of knowledge concerning internalization pathways for modified and unmodified oligonucleotides and how these pathways may affect the intracellular trafficking of oligonucleotides.KeywordsHerpes Simplex Virus TypeCellular InternalizationAcidic CompartmentPhosphorothioate OligosEndocytic UptakeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals (1990)

Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.
Trusts: Disposition between Life Tenant and Remainderman of Proceeds of Bonds Bought at a Premium or Discount (1936)

Trustees under a will purchased two lots of bonds at a premium, one of which had a call date and price; a callable preferred stock at a price above the call price; and bonds at a discount. The trustees amortized the premium bonds to the maturity date in one case and to the call date in the other. The stock was amortized over a period of five years to the call price. The life tenant claimed the right to be paid discount accumulated on the bonds bought at a discount. Held, that the action of the trustees as to amortization of both lots of premium bonds was proper; that there was no basis for amortization on stock, though callable, as on bonds; that accumulation on bonds bought at a discount could not be paid to the life tenant. Old Colony Trust Co. v. Comstock, (Mass. 1935) 195 N. E. 389.
Chlorotrimethylsilane Mediated Formation of ω-Allyl Esters of Aspartic And Glutamic Acids (1990)

Abstract The protection of the ω-carboxylic function of aspartic and glutamic acids by an allyl ester is advantageous because of its orthogonality with most protecting groups and its compatibility with a number of reagents. In this communication we describe a simple method using chlorotrimethylsilane in the presence of allyl alcohol which gives exclusively the ω-allyl esters of both aspartic and glutamic acids in excellent yield.
Percus–Yevick Equation for Hard Spheres with Surface Adhesion (1968)

It is shown that the Percus–Yevick approximation can be solved analytically for a potential consisting of a hard core together with a rectangular attractive well, provided that a certain limit is taken in which the range of the well becomes zero and its depth infinite. The results show a first-order phase transition which appears to be of the type observed numerically for the Lennard-Jones 12–6 potential.
Microcellular sheet extrusion system process design models for shaping and cell growth control (1998)

Abstract The feasibility of shaping a nucleated polymer/gas solution represents a significant advancement for microcellular plastics process technology. Through proper design of the foaming die, nucleated solution flows can be shaped to arbitary dimensions while maintaining the functional independence of cell nucleation, cell growth and shaping. To maintain funcational independence, stringent pressure and temperature design specifications, which supersede those of conventional foam processing, must be met by the foaming die design. As a means of aiding the design process, a model is developed for predicting pressure losses and flow rates of nucleated polymer/gas solutions. A comparison of the model predictions and the actual foaming die design performance shows good agreement for limited data. These relatively simple models capture the major physics of the complicated two‐phase flow field and provide a sound base from which scale‐up of the foaming die concept can be achieved. The nucleated polymer/gas solution flow models predict highly nonlinear volumetric flow rates contrasting constant flow rates predicted for the neat polymer flow. In addition, a convenient method for classifying nucleated polymer/gas solution flow is presented based on a dimensionless ratio of the characteristic flow rate to the characteristic gas diffusion rate.
AHA/ACC Guidelines for Preventing Heart Attack and Death in Patients With Atherosclerotic Cardiovascular Disease: 2001 Update (2001)

Since the original publication (in 1995) of the American Heart Association (AHA) consensus statement on secondary prevention, which was endorsed by the American College of Cardiology (ACC), important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease. As noted in that statement, aggressive risk factor management clearly improves patient survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients. The compelling evidence from some recent clinical trials was the impetus to revise the 1995 guidelines.
Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. (1998)

Epithelial ovarian cancer comprises three major histological subtypes (serous, mucinous, and endometrioid), and it is becoming clear that the developmental pathways for these subtypes are fundamentally different. In particular, endometrioid ovarian cancers probably arise by the malignant transformation of ectopic endometrial implants called endometriosis and not the ovarian surface epithelium. The PTEN/MMAC gene on chromosome 10q23 is a tumor suppressor implicated in the pathogenesis of a wide variety of malignancies, but to date, somatic mutations in PTEN have not been identified in studies of predominantly serous ovarian cancers. In endometrial cancers, PTEN mutations are very common in tumors of the endometrioid type but have rarely been found in serous types, and we hypothesized that a similar histological subtype bias might be occurring in ovarian cancer. We have analyzed 81 ovarian tumors, including 34 endometrioid, 29 serous, 10 mucinous, and 8 clear cell tumors, for loss of heterozygosity (LOH) on 10q23 and for mutations in all 9 coding exons of PTEN. LOH was common among the endometrioid (43%) and serous (28%) tumors but was infrequent among the other histological subtypes. Somatic PTEN mutations were detected in seven (21%) of the endometrioid tumors, and in all informative cases, the mutation was accompanied by loss of the wild-type allele. One mucinous tumor without 10q23 LOH was shown to harbor two somatic PTEN mutations. In this tumor, the histological appearance of the mucinous areas was atypical, and the mucinous areas contained foci of endometrioid differentiation. The majority of tumors with PTEN mutations were grade 1 and/or stage 1, suggesting that inactivation of PTEN is an early event in ovarian tumorigenesis. No PTEN mutations were found among the serous or clear cell tumors. The identification of frequent somatic PTEN mutations in endometrioid ovarian tumors indicates that it plays a significant role in the etiology of this subtype. The absence of mutations in other histological subtypes is consistent with the hypothesis that epithelial ovarian cancers arise through distinct developmental pathways.
The Physiologic Cipher at Altitude: Telemedicine and Real-Time Monitoring of Climbers on Mount Everest (2000)

Advanced wearable biosensors for vital-signs monitoring (physiologic cipher) are available to improve quality of healthcare in hospital, nursing home, and remote environments. The objective of this study was to determine reliability of vital-signs monitoring systems in extreme environments. Three climbers were monitored 24 hours while climbing through Khumbu Icefall. Data were transmitted to Everest Base Camp (elevation 17,800 feet) and retransmitted to Yale University via telemedicine. Main outcome measures (location, heart rate, skin temperature, core body temperature, and activity level) all correlated through time-stamped identification. Two of three location devices functioned 100% of the time, and one device failed after initial acquisition of location 75% of the time. Vital-signs monitors functioned from 95%-100% of the time, with the exception of one climber whose heart-rate monitor functioned 78% of the time. Due to architecture of automatic polling and data acquisition of biosensors, no climber was ever without a full set of data for more than 25 minutes. Climbers were monitored continuously in real-time from Mount Everest to Yale University for more than 45 minutes. Heart rate varied from 76 to 164 beats per minute, skin temperature varied from 5 to 10 degrees C, and core body temperature varied only 1-3 degrees C. No direct correlation was observed among heart rate, activity level, and body temperature, though numerous periods suggested intense and arduous activity. Field testing in the extreme environment of Mount Everest demonstrated an ability to track in real time both vital signs and position of climbers. However, these systems must be more reliable and robust. As technology transitions to commercial products, benefits of remote monitoring will become available for routine healthcare purposes.
Secretion of N-glycosylated interleukin-1 beta in Saccharomyces cerevisiae using a leader peptide from Candida albicans. Effect of N-linked glycosylation on biological activity (1991)

Human interleukin-1 beta (IL-1 beta) is expressed in activated monocytes as a 31-kDa precursor protein which is processed and secreted as a mature, unglycosylated 17-kDa carboxyl-terminal fragment, despite the fact that it contains a potential N-linked glycosylation site near the NH2 terminus (-Asn7-Cys8-Thr9-). cDNA coding for authentic mature IL-1 beta was fused to the signal sequence from the Candida albicans glucoamylase gene, two amino acids downstream from the signal processing site. Upon expression in Saccharomyces cerevisiae, approximately equimolar amounts of N-glycosylated (22 kDa) and unglycosylated (17 kDa) IL-1 beta protein were secreted. The N-glycosylated yeast recombinant IL-1 beta exhibited a 5-7-fold lower specific activity compared to the unglycosylated species. The mechanism responsible for inefficient glycosylation was also studied. We found no differences in secretion kinetics or processing between the two extracellular forms of IL-1 beta. The 17-kDa protein, which was found to lack core sugars, does not result from deglycosylation of the 22-kDa protein in vivo and does not result from saturation of the glycosylation enzymatic machinery through overexpression. Alteration of the uncommon Cys8 residue in the -Asn-X-Ser/Thr-glycosylation site to Ser also had no effect. However, increasing the distance between Asn7 and the signal processing site increased the extent of core N-linked glycosylation, suggesting a reduction in glycosylation efficiency near the NH2 terminus.
Single-Nucleotide Polymorphism–Based Noninvasive Prenatal Screening in a High-Risk and Low-Risk Cohort (2014)

II.