gebhart/patrepeval huggingface dataset:
A rationale for the design of an inhibitor of tyrosyl kinase. (1990)

Two gastrin analogs containing a D- and a L-tetrafluorinated tyrosyl residue (Arg-Arg-Leu-Glu-Glu-Glu-Glu-Glu-Ala-(F4)Tyr-Gly) were synthesized and tested as substrates and inhibitors of the insulin receptor kinase. No phosphorylation of these peptides was observed, but both gastrin analogs were effective inhibitors in the microM range. Although the D- and L-tetrafluorotyrosine-gastrin analogs differ in the sequence by only 1 amino acid residue, a different inhibitory pattern was obtained with the insulin receptor. The inhibition of all-L-isomer is competitive with respect to both the protein substrate, reduced, S-carboxymethylated, and maleylated lysozyme (RCMM-lysozyme), and ATP with a Ki value of 4 microM. This result corroborates a previous finding (Walker, D. H., Kuppuswamy, D., Visvanathan, A., and Pike, L. J. (1987) Biochemistry 26, 1428-1433) that the kinetic mechanism for insulin receptor is a random Bi Bi mechanism. Different from the L-isomer, the D-analog is competitive to RCMM-lysozyme and noncompetitive toward ATP and gives an apparent inhibition constant of 20 microM. A free tetrafluorotyrosine also shows a competitive inhibition to protein substrate, RCMM-lysozyme (Ki = 18 mM) whereas free tyrosine shows no effect on the activity of insulin receptor. These results show the importance of the charge state and nucleophilicity of the phenolic component in substrate recognition and catalysis and provide a rationale for the design of inhibitors of tyrosyl phosphorylation.
Two acid‐inducible promoters from Lactococcus lactis require the cis‐acting ACiD‐box and the transcription regulator RcfB (2005)

We previously characterized three Lactococcus lactis promoters, P170, P1 and P3, which are induced by low pH. Here, we identified a novel 14 bp regulatory DNA region centred at around -41.5 and composed of three tetranucleotide sequences, boxes A, C and D. Boxes A and C contribute to P1 activity, whereas box D and the position of boxes ACD (renamed ACiD-box) are essential to P1 activity and acid response. We also identified a trans -acting protein, RcfB, which is involved in P170 and P1 basal activity and is essential for their pH induction. The regulator belongs to the Crp-Fnr family of transcription regulators. Overexpression of rcfB resulted in increased beta-galactosidase activities and lantibiotic lacticin 481 production from P170- and P1-controlled genes, respectively, in acid condition. RcfB is thus probably activated when cells encounter an acid environment. rcfB is co-transcribed with genes encoding an universal stress-like protein and a multidrug transporter. RcfB plays a role in acid adaptation, as the survival rate of an rcfB mutant after a lethal acid challenge was 130-fold lower than that of the wild-type strain, when the bacteria were first grown in acidic medium. The groESL promoter includes a sequence resembling an ACiD-box and the chaperone GroEL production is partly RcfB dependent in acid condition. Our results suggest that the ACiD-box could be the DNA target site of RcfB.
Pruning algorithms-a survey (1993)

A rule of thumb for obtaining good generalization in systems trained by examples is that one should use the smallest system that will fit the data. Unfortunately, it usually is not obvious what size is best; a system that is too small will not be able to learn the data while one that is just big enough may learn very slowly and be very sensitive to initial conditions and learning parameters. This paper is a survey of neural network pruning algorithms. The approach taken by the methods described here is to train a network that is larger than necessary and then remove the parts that are not needed.
Multiplexed optical fibre strain sensing using cross-correlationof subcarrier interferometric spectra (1996)

A novel technique for evaluating strain in multiple long-length sections of optical fibre is described. Sections defined by reflective markers are interrogated with subcarrier interferometry. Path-length changes are monitored using cross-correlation. A resolution of 35 µm has been obtained over 5 m sensing sections, together with inter-section crosstalk levels below -45 dB.
Los campesinos del Caribe: Una perspectiva dominicana* (2014)

En este artÃ­culo se ofrece una interpretaciÃ³n sobre la evoluciÃ³n histÃ³rica del campesinado en la RepÃºblica Dominicana. Se argumenta que las clases campesinas jugaron papeles fundamentales en el desarrollo econÃ³mico y social de ese paÃ­s caribeÃ±o. AdemÃ¡s, se ofrece una visiÃ³n comparativa sobre el campesinado dominicano, que es contrastado con el campesinado en otros paÃ­ses del Caribe y de AmÃ©rica Latina.
Silencing of the mammary-derived growth inhibitor (MDGI) gene in breast neoplasms is associated with epigenetic changes. (1996)

Recently, we reported that breast cancer cell lines fail to express the gene encoding the fatty acid binding protein mammary derived growth inhibitor (MDGI) and that transfection with an MDGI expression vector results in suppression of the malignant phenotype, suggesting that MDGI is a tumor suppressor gene. We also demonstrated that homozygous deletion and point mutation are not common mechanisms for silencing of the MDGI gene in human breast neoplasms. We now report that hypermethylation of HpaII and HhaI sites upstream of the first exon of the MDGI gene, and a SacII site in the first intron, occurs frequently in human breast cancer cell lines. This distinct methylation pattern is associated with loss of transcription and is reversible by treatment with 5-aza-deoxycytidine. Primary breast tumors also exhibited methylation of the SacII site (19 of 35, 54.3%) and the HpaII and HhaI sites (21 of 35, 66%). Hypermethylation of these sites was correlated with the absence of MDGI mRNA in these tumors. Our results suggest that epimutation of the MDGI gene leads to silencing, which, in turn, may initiate or contribute to progression of breast cancer.
Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A (2008)

To assemble mitotic spindles, cells nucleate microtubules from a variety of sources including chromosomes and centrosomes. We know little about how the regulation of microtubule nucleation contributes to spindle bipolarity and spindle size. The Aurora A kinase activator TPX2 is required for microtubule nucleation from chromosomes as well as for spindle bipolarity. We use bacterial artificial chromosome-based recombineering to introduce point mutants that block the interaction between TPX2 and Aurora A into human cells. TPX2 mutants have very short spindles but, surprisingly, are still bipolar and segregate chromosomes. Examination of microtubule nucleation during spindle assembly shows that microtubules fail to nucleate from chromosomes. Thus, chromosome nucleation is not essential for bipolarity during human cell mitosis when centrosomes are present. Rather, chromosome nucleation is involved in spindle pole separation and setting spindle length. A second Aurora A-independent function of TPX2 is required to bipolarize spindles.
New Insight into the Formation of Hybrid Perovskite Nanowires via Structure Directing Adducts (2016)

We report a facile preparation approach of MAPbBr3, MAPbCl3, or FAPbBr3 (where MA = CH3NH3+ and FA = CH(NH2)2+) perovskite nanowires via sequential synthesis of MAPbI3 and FAPbI3 nanowires with chemically controlled composition and morphologies followed by an exchange of halide anions. The nanowires formation sequence includes intermediate phases such as MAI-PbI2-DMF and FAI-PbI2-DMF (DMF = dimethylformamide) acting as structure directing agent. The 1D shape of the adduct is preserved during the conversion to perovskite. The adducts play the role of key precursors controlling the final product morphology. Systematic investigations of the observed phase transformations and morphology features on multiple length scales revealed the effectiveness of the suggested synthetic route utilizing an original pseudomorph formation mechanism of the 1D structures to produce partly oriented films and textured layers of the nanowires via only a few experimental steps.
Repacking protein cores with backbone freedom: structure prediction for coiled coils. (1995)

Progress in homology modeling and protein design has generated considerable interest in methods for predicting side-chain packing in the hydrophobic cores of proteins. Present techniques are not practically useful, however, because they are unable to model protein main-chain flexibility. Parameterization of backbone motions may represent a general and efficient method to incorporate backbone relaxation into such fixed main-chain models. To test this notion, we introduce a method for treating explicitly the backbone motions of alpha-helical bundles based on an algebraic parameterization proposed by Francis Crick in 1953 [Crick, F. H. C. (1953) Acta Crystallogr. 6, 685-689]. Given only the core amino acid sequence, a simple calculation can rapidly reproduce the crystallographic main-chain and core side-chain structures of three coiled coils (one dimer, one trimer, and one tetramer) to within 0.6-A root-mean-square deviations. The speed of the predictive method [approximately 3 min per rotamer choice on a Silicon Graphics (Mountain View, CA) 4D/35 computer] permits it to be used as a design tool.
Workflow enactment with continuation and future objects (2002)

An increasing number of software developers are turning to workflow to separate the logic and the control aspects in their applications, thus making them more amenable to change. However, in spite of recent efforts to standardize and provide reusable workflow components, many developers build their own. This is a challenging endeavor and involves solving problems which seem incompatible with the object paradigm and current object-oriented programming languages. In the context of an object-oriented workflow framework, this paper demonstrates a novel approach that resolves this impedance mismatch with techniques drawn from programming language theory. This successful cross-pollination narrows the gap between the results of decades of research in programming languages and developers working hard to cope with change.
Current Treatment and Clinical Trial Developments for Ductal Carcinoma In Situ of the Breast (2007)

Ductal carcinoma in situ (DCIS) is the fastest growing subtype of breast cancer, mainly because of the aging of our populations and improvements in diagnostic mammography and core biopsy. DCIS represents a proliferation of malignant-appearing cells that have not invaded beyond the ductal basement membrane and is a precursor for the development of invasive breast cancer (IBC). Approximately 40% of patients with DCIS treated with biopsy alone, without complete excision or further therapy, develop IBC. Most DCIS itself is harmless if it is detected and excised before it can progress to IBC, and the current approach to DCIS treatment is aimed at just that goal. Typically, it consists of multimodal treatment including segmental mastectomy followed by radiation therapy to the whole breast and then hormonal therapy or total mastectomy followed by hormonal therapy. This review discusses the state-of-the-art in DCIS detection and treatment and highlights promising new strategies in the care of DCIS patients. The data regarding the effectiveness of breast-conserving surgery versus total mastectomy, the possible avoidance of radiation therapy in some subgroups of patients, and the role of hormonal agents are reviewed. Neoadjuvant therapy and the use of trastuzumab for DCIS are currently under investigation and may be future treatment options for DCIS.
Fluorine-19 substituent chemical shifts (SCS) (1970)

A number of substituted aryl fluorides have been synthesized and their fluorine-19 substituent chemical shifts (scs) have been measured. The comparison of the scs of 1-( m -fluorophenyl)propan-2-one, 1-(p-fluorophenyl)propan-2-one, 7-fluorotetral-2-one, and 6-fluorotetral-2-one confirm Dewarsl-3 conclusions that long-range non-mesomeric effects are transmitted through space and that this polar effect makes a considerable contribution to the overall 19F scs in aromatic systems. It is also shown that the fluorine substituent chemical shifts of +F+M substituents in 7-substituted 2-fluoronaphthalenes (7β) can be interpreted in terms of a modified FM treatment. The mesomeric-field effect is shown to be important in this disposition (78) of naphthalene.
Designing for improved social responsibility, user participation and content in on-line communities (2002)

Web sites face difficult challenges in supporting successful communities. In this paper we discuss 2 operating web sites, identically designed but with different and distinct audiences. These sites collect user data from site activity and feed it back to the user community in novel ways. The sites are highly active and growing, and have fostered socially conscious, easily navigable and comprehensible on-line communities with little cost and maintenance. The practice of user data collection and re-purposing we describe works particularly well in highly contextual or information /resource-driven communities. These sites also integrate custom content authoring tools and track their use. The authoring tools were designed to quickly grow a specialized base of content created by users and published to a larger audience. A status system encourages the participation of users to contribute to this knowledge base, while increasing social awareness and responsibility in areas of high user interaction. All user activity, communications, and feedback are tracked. Then data is compiled and re-incorporated into scalable solutions for better navigability, content filtering, and presentation of contents to a larger audience. This practice creates a uniquely high quality of interaction within web communities
Reconstituted collagen is not capable of activating factor XII but causes intrinsic coagulation by activating platelets (1992)

Using a rheological technique to measure the coagulation of plasma in collagen-coated tubes, we studied the intrinsic coagulant activities of different types (I, III, IV and V) and structures of reconstituted collagen. Recalcified, platelet-free plasma (PFP) in contact with the collagen surface did not clot, irrespective of the type and structure of collagen. Coagulation of platelet-rich plasma (PRP) did occur, although the time of onset of coagulation was highly dependent on the type and structure of the collagen used. Coagulation of PRP occurred rapidly on a collagen surface consisting of highly ordered fibrils (banded structure) to which large numbers of aggregated platelets adhered with shape change. In contrast, initiation of coagulation was delayed in PRP after incubation with 5 mM dibutyrylcyclic AMP (DB-cAMP) for 50 min. Coagulation of PRP was completely suppressed after 30 min incubation with colchicine (5.0 mg/ml). This suggested that disruption of platelet microtubules completely suppressed the stimulation of platclets associated with the initiation of intrinsic coagulation on the collagen surface. We conclude that reconstituted collagen is not capable of activating factor XII. Initiation of coagulation of recalcified PRP in contact with the reconstituted collagen surface is caused by the activation of platelets.
Safety and efficacy of weekly 5-fluorouracil/ folinic acid/oxaliplatin/irinotecan in the first-line treatment of gastrointestinal cancer (2010)

These data show excellent tolerance and efficacy of the FUFOXIRI regimen in both mCRC and GC. Therefore, FUFOXIRI is a promising backbone for future studies incorporating biologic 'targeted' agents for the treatment of gastrointestinal cancers.
Microscale acoustofluidics: Microfluidics driven via acoustics and ultrasonics (2011)

This article reviews acoustic microfluidics: the use of acoustic fields, principally ultrasonics, for application in microfluidics. Although acoustics is a classical field, its promising, and indeed perplexing, capabilities in powerfully manipulating both fluids and particles within those fluids on the microscale to nanoscale has revived interest in it. The bewildering state of the literature and ample jargon from decades of research is reorganized and presented in the context of models derived from first principles. This hopefully will make the area accessible for researchers with experience in materials science, fluid mechanics, or dynamics. The abundance of interesting phenomena arising from nonlinear interactions in ultrasound that easily appear at these small scales is considered, especially in surface acoustic wave devices that are simple to fabricate with planar lithography techniques common in microfluidics, along with the many applications in microfluidics and nanofluidics that appear through the literature.
R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein (2017)

The R2TP/Prefoldin-like (R2TP/PFDL) complex has emerged as a cochaperone complex involved in the assembly of a number of critical protein complexes including snoRNPs, nuclear RNA polymerases and PIKK-containing complexes. Here we report on the use of multiple target affinity purification coupled to mass spectrometry to identify two additional complexes that interact with R2TP/PFDL: the TSC1-TSC2 complex and the U5 small nuclear ribonucleoprotein (snRNP). The interaction between R2TP/PFDL and the U5 snRNP is mostly mediated by the previously uncharacterized factor ZNHIT2. A more general function for the zinc-finger HIT domain in binding RUVBL2 is exposed. Disruption of ZNHIT2 and RUVBL2 expression impacts the protein composition of the U5 snRNP suggesting a function for these proteins in promoting the assembly of the ribonucleoprotein. A possible implication of R2TP/PFDL as a major effector of stress-, energy- and nutrient-sensing pathways that regulate anabolic processes through the regulation of its chaperoning activity is discussed.
Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. (1994)

Analysis of previously unknown genetic aberrations in solid tumors has become possible through the use of comparative genomic hybridization (CGH), which is based on competitive binding of tumor and control DNA to normal metaphase chromosomes. CGH allows detection of DNA sequence copy number changes (deletions, gains, and amplifications) on a genome-wide scale in a single hybridization. We describe here an improved CGH technique, which enables reliable detection of copy number changes in archival formalin-fixed paraffin-embedded tumor samples. The technique includes a modified DNA extraction protocol, which produces high molecular weight DNA which is necessary for high quality CGH. The DNA extraction includes a 3-day digestion with proteinase K, which remarkably improves the yield of high molecular weight DNA. Labeling of the test DNA with a directly fluorescein-conjugated nucleotide (instead of biotin labeling) improved significantly the quality of hybridization. Using the paraffin-block technique, we could analyze 70 to 90% of paraffin blocks, including very old samples as well as samples taken at autopsy. CGH from paraffin blocks was highly concordant (95%) with analyses done from matched freshly frozen tumor samples (n = 5 sample pairs; kappa coefficient = 0.83). The method described here has wide applicability in tumor pathology, allowing large retrospective prognostic studies of genetic aberrations as well as studies on genetic pathogenesis of solid tumors, inasmuch as premalignant lesions and primary and metastatic tumors can be analyzed by using archival paraffin-embedded samples.
Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies (2001)

Chromosomal translocation t(6;14)(p21.1;q32.3) has been reported as a rare but recurrent event not only in myeloma and plasma cell leukemia but also in diffuse large B-cell non-Hodgkin lymphoma (B-NHL) (diffuse large B-cell lymphoma [DLBCL]) and splenic lymphoma with villous lymphocytes (SLVL); however, the nature of the target gene(s) has not been determined. This study identified t(6;14)(p21.1;q32.3) in 3 cases of transformed extranodal marginal zone B-NHL, in 1 case of SLVL, and in 1 case of a low-grade B-cell lymphoproliferative disorder. In a sixth case, a CD5(+) DLBCL, the translocation was identified by molecular cloning in the absence of cytogenetically detectable change. Two chromosomal translocation breakpoints were cloned by using long-distance inverse polymerase chain reaction methods. Comparison with the genomic sequence for chromosome 6p21.1 showed breakpoints approximately 59 and 73.5 kilobases 5' of the cyclin D3 (CCND3) gene with no other identifiable transcribed sequences in the intervening region. Although Southern blotting with derived genomic 6p21.1 probes failed to detect other rearrangements, fluorescent in situ hybridization assays, using BAC (bacterial artificial chromosome) clones spanning and flanking the CCND3 locus, along with probes for IGH confirmed localization of 6p21.1 breakpoints within the same region, as well as fusion of the CCND3 and IGH loci. Furthermore, in all cases, high-level expression of CCND3 was demonstrated at RNA and/or protein levels by Northern and Western blotting and by immunohistochemistry. These data implicate CCND3 as a dominant oncogene in the pathogenesis and transformation in several histologic subtypes of mature B-cell malignancies with t(6;14)(p21.1;q32.3) and suggest that CCND3 overexpression seen in about 10% of DLBCL cases may have a genetic basis.
Room-temperature operation of InAs quantum-dash lasers on InP [001] (2001)

The first self-assembled InAs quantum dash lasers grown by molecular beam epitaxy on InP (001) substrates are reported. Pulsed room-temperature operation demonstrates wavelengths from 1.60 to 1.66 μm for one-, three-, and five-stack designs, a threshold current density as low as 410 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> for singlestack uncoated lasers, and a distinctly quantum-wire-like dependence of the threshold current on the laser cavity orientation. The maximal modal gains for lasing in the ground-state with the cavity perpendicular to the dash direction are determined to be 15 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">–1</sup> for single-stack and 22 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">–1</sup> for five-stack lasers.