gebhart/patrepeval huggingface dataset:
The cystatins: Protein inhibitors of cysteine proteinases (1991)

The last decade has witnessed enormous progress of protein inhibitors of cysteine proteinases concerning their structures, functions and evolutionary relationships. Although they differ in their molecular properties and biological distribution, they are structurally related proteins. All three inhibitory families, the stefins, the cystatins and the kininogens, are members of the same superfamily. Recently determined crystal structures of chicken cystatin and human stefin B established a new mechanism of interaction between cysteine proteinases and their inhibitors which is fundamentally different from the standard mechanism for serine proteinases and their inhibitors.
The chemistry of metathesized soybean oil (1999)

Abstract New materials derived from metathesized soybean oil have been prepared and characterized. Thermal polymerization of metathesized soybean oil in the presence of air results in yellow, brittle gels. These materials display a curious tendency to produce audible popping sounds when exposed to chlorinated organic solvents, such as chloroform or dichloromethane. Complete hydrogenation of metathesized soybean oil has been accomplished in excellent yields utilizing 10% palladium on carbon in dichloromethane. A new, very mild, effective epoxidation procedure for soybean oil, utilizing methyltrioxorhenium (VII) (MTO) and pyridine as the catalyst system and hydrogen peroxide as the oxidant, has been developed. This epoxidation reaction affords excellent yields of epoxidized soybean oil with some control of the degree of epoxidation at very low MTO concentrations (&lt; 0.5 mol%). This reaction is also very effective for the epoxidation of metathesized soybean oil to higher molecular weight epoxidized soybean oil materials.
Mammographic density is related to stroma and stromal proteoglycan expression (2003)

Alteration in stromal composition is correlated with increased mammographic density. Although epithelial changes define the eventual pathway for breast cancer development, mammographic density might correspond more directly to alterations in stromal composition.
Separation of cells by velocity sedimentation (1969)

Abstract A system for fractionating populations of living cells by velocity sedimentation in the earth's gravitational field is described. The cells start in a thin band near the top of a shallow gradient of 3% to 30% fetal calf serum in phosphate buffered saline at 4°C. Cell separation takes place primarily on the basis of size and is approximately independent of cell shape. A sharply‐defined upper limit, called the streaming limit, exists for the cell concentration in the starting band beyond which useful cell separations cannot be achieved. This limit, which varies with the type of cell being sedimented, can be significantly increased by proper choice of gradient shape. For sheep erythrocytes (sedimentation velocity of 1.6 mm/hour) it is 1.5 × 10 7 cells/ml. Measured and calculated sedimentation velocities for sheep erythrocytes are shown to be in agreement. The technique is applied to a suspension of mouse spleen cells and it is shown, using an electronic cell counter and pulse height analyzer, that cells are fractionated according to size across the gradient such that the sedimentation velocity (in mm/hour) approximately equals r 2 /4 where r is the cell radius in microns. Since cells of differing function also often differ in size, the system appears to have useful biological applications.
Hepatitis C Virus Drives the Unconstrained Monoclonal Expansion of VH1–69-Expressing Memory B Cells in Type II Cryoglobulinemia: A Model of Infection-Driven Lymphomagenesis (2005)

Chronic hepatitis C virus infection causes B cell lymphoproliferative disorders that include type II mixed cryoglobulinemia and lymphoma. This virus drives the monoclonal expansion and, occasionally, the malignant transformation of B cells producing a polyreactive natural Ab commonly encoded by the V(H)1-69 variable gene. Owing to their property of producing natural Ab, these cells are reminiscent of murine B-1 and marginal zone B cells. We used anti-Id Abs to track the stages of differentiation and clonal expansion of V(H)1-69(+) cells in patients with type II mixed cryoglobulinemia. By immunophenotyping and cell size analysis, we could define three discrete stages of differentiation of V(H)1-69(+) B cells: naive (small, IgM(high)IgD(high)CD38(+)CD27(-)CD21(high)CD95(-)CD5(-)), "early memory" (medium-sized, IgM(high)IgD(low)CD38(-)CD27(+)CD21(low)CD95(+)CD5(+)), and "late memory" (large-sized, IgM(low)IgD(low-neg)CD38(-)CD27(low)CD21(low-neg)CD5(-)CD95(-)). The B cells expanded in cryoglobulinemia patients have a "memory" phenotype; this fact, together with the evidence for intraclonal variation, suggests that antigenic stimulation by hepatitis C virus causes the unconstrained expansion of activated V(H)1-69(+) B cells. In some cases, these cells replace the entire pool of circulating B cells, although the absolute B cell number remains within normal limits. Absolute monoclonal V(H)1-69(+) B lymphocytosis was seen in three patients with cryoglobulinemia and splenic lymphoma; in two of these patients, expanded cells carried trisomy 3q. The data presented here indicate that the hepatitis C virus-driven clonal expansion of memory B cells producing a V(H)1-69(+) natural Ab escapes control mechanisms and subverts B cell homeostasis. Genetic alterations may provide a further growth advantage leading to an overt lymphoproliferative disorder.
Distribution of fibronectin isoforms in human renal disease (2001)

Fibronectin (FN) is an extracellular matrix component which appears in different isoforms, due to alternative mRNA splicing of the ED-A, ED-B, and IIICS regions, and subsequent post-translational modifications. The FN isoforms, some of which occur specifically during fetal development and in fibrogenic diseases, have been reported to play a role in various biological functions, such as regulation of the matrix assembly, adhesion, and proliferation. The contribution of these FN isoforms to the pathogenesis of chronic renal diseases, which are also fibrogenic disorders, is not well known. This study therefore examined the distribution of FN isoforms in renal diseases by immunohistochemistry, with a panel of isoform-specific monoclonal antibodies (MAbs), applied to 63 abnormal renal biopsies and ten normal controls. Normal kidneys contained total FN (MAb IST4) both in the mesangial and in the interstitial extracellular matrix (ECM), but only traces of ED-A-positive FN (MAb IST9), and no ED-B-positive FN (MAb BC1) or oncofetal FN (MAb FDC6) was found in normal renal tissue. All patients with renal disease demonstrated increased total FN staining of the interstitium and the mesangium. Periglomerular fibrotic lesions and fibrous crescents showed massive accumulation of total FN, whereas the amount of total FN in the ECM of obsolescent glomeruli was decreased, compared with that in normal mesangial ECM. Oncofetal (FDC6), EDB-negative (MAb IST6), ED-A-positive, and ED-B-positive FN isoforms were found in glomerular ECM accumulations and in fibrous crescents. Tubulointerstitial fibrotic lesions predominantly contained the ED-A-positive FN isoform, whereas in globally sclerotic glomeruli, predominantly ED-B-positive FN was observed. The expression of FN isoforms was similar in all renal diseases studied. These results show that in various renal diseases, oncofetal (FDC6) FN and ED-A- and ED-B-positive isoforms of FN accumulate at locations of chronic lesions, independently of the aetiology of the disease. The deposition of these isoforms in human renal tissue may play a role in the modulation of the immune response by attracting monocytes and lymphocytes to the injured kidney. Furthermore, because the ED-B-positive FN isoform is highly susceptible to proteolytic degradation, its accumulation may play a role in scar formation and tissue repair. ED-B-positive FN forms a temporary scaffold supporting the cells, which can easily be cleared by proteolytic degradation once new tissue has been produced at the site of injury.
On the Role of the cAMP Response Element Binding Protein in Long-Term Cardiac Memory (2003)

To the Editor:Cardiac memory (CM) has been investigated extensively over the last decades. 1-3Whereas early studies focused on electrotonus as a central determinant of cardiac memory, 3 more recent work has considered changes in ion channels driven by to-be-determined transcriptional events. 4,5However, any transcriptional mechanisms involved remained largely unidentified.In the September 5 issue of the journal, we reported our first study investigating transcriptional mechanisms of CM. 6 Based on previously shown parallels between CM and memory in the CNS, 7 which incorporates the cAMP response element binding protein (CREB) as an important transcription factor, 8 we investigated the role of CREB in CM.Briefly, using 2 hours of ventricular pacing (VP) to induce short-term CM (STCM), we observed a decrease in nuclear CREB, with phosphorylated CREB levels remaining equal.This decrease was most marked close to the pacing electrode.We also showed reduced binding of nuclear proteins to CRE in dogs in which LTCM was induced by 3 weeks of VP and demonstrated binding of nuclear proteins to a CRE-like element in the Kv4.3 promoter.An erudite editorial by Folco et al 9 in the same issue of the journal notes that several members of the CREB family of transcription factors (including CREM and ATF-1) can compensate for a loss of CREB.They also state that a 50% reduction in CREB is not necessarily adequate to cause loss of function.We fully agree with both points, and accordingly never stated that the 50% CREB reduction observed during 2 hours of VP is responsible for STCM or uniquely responsible for LTCM.However, we do believe and did state (see page 477) that this reduction in CREB might initiate a cascade of events leading to LTCM.It remains to be elucidated whether LTCM would result from events downstream from CREB or from a direct influence of CREB on CM target genes (such as Kv4.3). 4 In support of the latter possibility was our observation of nuclear protein binding activity to a CRE-like element in the Kv4.3 promoter region.Folco and colleagues 9 state the Kv4.3 CRE (TGACGTCT) lacks the complete CRE core sequence (CGTCA), and on initial inspection this might seem the case.However, the complementary strand of the Kv4.3 sequence is 5Ј-AGACGTCA-3Ј, which does contain a CRE core sequence.Whether this element has comparable binding capacities as the consensus CRE is currently under investigation.Folco and colleagues were puzzled, as were we, that no increase in phosphorylated CREB occurred early in the 2 hours of VP.They offer the explanation that increased phosphorylation might be ob-
Structural basis for dual specificity of yeast N-terminal amidase in the N-end rule pathway (2016)

The first step of the hierarchically organized Arg/N-end rule pathway of protein degradation is deamidation of the N-terminal glutamine and asparagine residues of substrate proteins to glutamate and aspartate, respectively. These reactions are catalyzed by the N-terminal amidase (Nt-amidase) Nta1 in fungi such as Saccharomyces cerevisiae, and by the glutamine-specific Ntaq1 and asparagine-specific Ntan1 Nt-amidases in mammals. To investigate the dual specificity of yeast Nta1 (yNta1) and the importance of second-position residues in Asn/Gln-bearing N-terminal degradation signals (N-degrons), we determined crystal structures of yNta1 in the apo state and in complex with various N-degron peptides. Both an Asn-peptide and a Gln-peptide fit well into the hollow active site pocket of yNta1, with the catalytic triad located deeper inside the active site. Specific hydrogen bonds stabilize interactions between N-degron peptides and hydrophobic peripheral regions of the active site pocket. Key determinants for substrate recognition were identified and thereafter confirmed by using structure-based mutagenesis. We also measured affinities between yNta1 (wild-type and its mutants) and specific peptides, and determined K<sub>M</sub> and k<sub>cat</sub> for peptides of each type. Together, these results elucidate, in structural and mechanistic detail, specific deamidation mechanisms in the first step of the N-end rule pathway.
The Oxidation of Shaped Silicon Surfaces (1982)

Nonplanar silicon surfaces were prepared and oxidized at 900°–1100°C and the oxide morphology was studied by transmission electron microscopy of thin sections. A 30% decrease in oxide thickness at silicon step edges following 900° and 950°C wet oxidation is attributed to the effect of locally compressive intrinsic stress within the oxide on the solubility of oxygen. Oxidation inhibition becomes less at higher temperatures due to the relief of stress (during growth) by viscous flow of the oxide.
Improving system performance in case-based iterative optimization through knowledge filtering (1995)

Adding knowledge to a knowledge-based system is not monotonically beneficial. We discuss and experimentally validate this observation in the context of CABINS, a system that learns control knowledge for iterative repair in ill-structured optimization problems. In CABINS, situation-dependent user&amp;apos;s decisions that guide the repair process are captured in cases together with contextual problem information. During iterative revision in CABINS, cases are exploited for both selection of repair actions and evaluation of repair results. In this paper, we experimentally demonstrated that unfiltered learned knowledge can degrade problem solving performance. We developed and experimentally evaluated the effectiveness of a set of knowledge filtering strategies that are designed to increase problem solving efficiency of the intractable iterative optimization process without sacrificing solution quality. These knowledge filtering strategies utilize progressive case base retrievals and failure inform...
Learning XML (2001)

From the Publisher:
The arrival of support for XMLthe Extensible Markup Languagein browsers and authoring tools has followed a long period of intense hype. Major databases, authoring tools (including Microsoft's Office 2000), and browsers are committed to XML support. Many content creators and programmers for the Web and other media are left wondering, What can XML and its associated standards really do for me? Getting the most from XML requires being able to tag and transform XML documents so they can be processed by web browsers, databases, mobile phones, printers, XML processors, voice response systems, and LDAP directories, just to name a few targets. 
In Learning XML, the authors explain XML and its capabilities succinctly and professionally, with references to real-life projects and other cogent examples. Learning XML shows the purpose of XML markup itself, the CSS and XSL styling languages, and the XLink and XPointer specifications for creating rich link structures. 
The basic advantages of XML over HTML are that XML lets a web designer define tags that are meaningful for the particular documents or database output to be used, and that it enforces an unambiguous structure that supports error-checking. XML supports enhanced styling and linking standards (allowing, for instance, simultaneous linking to the same document in multiple languages) and a range of new applications. 
For writers producing XML documents, this book demystifies files and the process of creating them with the appropriate structure and format. Designers will learn what parts of XML are most helpful to their team and will get started on creating Document Type Descriptions. For programmers, the book makes syntax and structures clear. It also discusses the stylesheets needed for viewing documents in the next generation of browsers, databases, and other devices. 

About the Authors:
Erik Ray is a software wrangler for the computer book publisher O'Reilly and Associates, helping to move production to an XML-based workflow. He lives with his wife Jeannine and 5 birds in Saugus, Massachusetts. When not writing, he can be found practicing kendo, watching Japanese animation, playing go, or stalking antiquarian book fairs to indulge his fetish for 19th-century children's books and machine bolt catalogs. 
Chris Maden left Brown University in 1994 and stumbled into a career in structured markup via a technical support position at Electronic Book Technologies in Providence, RI, creators of one of the first electronic book browsers, DynaText. There, he got involved in standards work, including participating in the first work on XML. From EBT, he staggered north to the Tools Group at O'Reilly, where he helped develop a new generation of SGML and XML publishing tools, and where he also joined the XSL Working Group at the W3C. In 1999, he left to join Yomu, an e-books startup in San Francisco, where he currently lives with his wife Ellie Fountain Maden.
Improved QR Code Localization Using Boosted Cascade of Weak Classifiers (2015)

Usage of computer-readable visual codes became common in our everyday life at industrial environments and private use. The reading process of visual codes consists of two tasks: localization and data decoding. Unsupervised localization is desirable at industrial setups and for visually impaired people. This paper examines localization efficiency of cascade classifiers using Haar-like features, Local Binary Patterns and Histograms of Oriented Gradients, trained for the finder patterns of QR codes and for the whole code region as well, and proposes improvements in post-processing.
Recovering reflectance and illumination in a world of painted polyhedra (2002)

To be immune to variations in illumination, a vision system needs to be able to decompose images into their illumination and surface reflectance components. Most computational studies thus far have been concerned with strategies for solving the problem in the restricted domain of 2-D Mondrians. This domain has the simplifying characteristic of permitting discontinuities only in the reflectance distribution while the illumination distribution is constrained to vary smoothly. Such approaches prove inadequate in a 3-D world of painted polyhedra which allows for the existence of discontinuities in both the reflectance and illumination distributions. The authors propose a two-stage computational strategy for interpreting images acquired in such a domain. The first stage attempts to use simple local gray-level junction analysis to classify the observed image edges into the illumination or reflectance categories. Subsequent processing verifies the global consistency of these local inferences while also reasoning about the 3-D structure of the object and the illumination source direction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Duplex Proximity Sequencing (Pro-Seq): A method to improve DNA sequencing accuracy without the cost of molecular barcoding redundancy (2017)

Abstract A challenge in the clinical adoption of cell-free DNA (cfDNA) liquid biopsies for cancer care is their high cost compared to potential reimbursement. The most common approach used in liquid biopsies to achieve high specificity detection of circulating tumor DNA (ctDNA) among a large background of normal cfDNA is to attach molecular barcodes to each DNA template, amplify it, and then sequence it many times to reach a low-error consensus. In applications where the highest possible specificity is required, error rate can be lowered further by independently detecting the sequences of both strands of the starting cfDNA. While effective in error reduction, the additional sequencing redundancy required by such barcoding methods can increase the cost of sequencing up to 100-fold over standard next-generation sequencing (NGS) of equivalent depth. We present a novel library construction and analysis method for NGS that achieves comparable performance to the best barcoding methods, but without the increase in sequencing and subsequent sequencing cost. Named Proximity-Sequencing (Pro-Seq), the method merges multiple copies of each template into a single sequencing read by physically linking the molecular copies so they seed a single sequencing cluster. Since multiple DNA copies of the same template are compared for consensus within the same cluster, sequencing accuracy is improved without the use of redundant reads. Additionally, it is possible to represent both senses of the starting duplex in a single cluster. The resulting workflow is simple, and can be completed by a single technician in a work day with minimal hands on time. Using both cfDNA and cell line DNA, we report the average per-mutation detection threshold and per-base analytical specificity to be 0.003% and &gt;99.9997% respectively, demonstrating that Pro-Seq is among the highest performing liquid biopsy technologies in terms of both sensitivity and specificity, but with greatly reduced sequencing costs compared to existing methods of comparable accuracy.
An Optimized Clinical Regimen for the Oncolytic Virus PV701 (2007)

Using slow infusion, patient tolerability was improved, while the first dose was safely escalated relative to two previous PV701 trials. Based on improved tolerability and encouraging signs of activity, this slow infusion regimen was selected for further PV701 clinical development.
Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V–Cy5.5 conjugate (2004)

In vivo imaging of treatment responses at the molecular level could have a significant impact on the speed of drug discovery and ultimately lead to personalized medicine. Strong interest has been shown in developing quantitative fluorescence-based technologies with good molecular specificity and sensitivity for noninvasive 3D imaging through tissues and whole animals. We show herein that tumor response to chemotherapy can be accurately resolved by fluorescence molecular tomography (FMT) with a phosphatidylserine-sensing fluorescent probe based on modified annexins. We observed at least a 10-fold increase of fluorochrome concentration in cyclophosphamide-sensitive tumors and a 7-fold increase of resistant tumors compared with control studies. FMT is an optical imaging technique developed to overcome limitations of commonly used planar illumination methods and demonstrates higher quantification accuracy validated by histology. It is further shown that a 3-fold variation in background absorption heterogeneity may yield 100% errors in planar imaging but only 20% error in FMT, thus confirming tomographic imaging as a preferred tool for quantitative investigations of fluorescent probes in tissues. Tomographic approaches are found essential for small-animal optical imaging and are potentially well suited for clinical drug development and monitoring.
[Evaluation of the effect of the sodium hyaluronate ophthalmic solution on tear film stability--non-contact specular microscopic evaluation]. (1993)

Sodium hyaluronate solution is known to relieve various dry eye symptoms by suppressing the breakup of the preocular tear film. Using tear film stability as a parameter, we examined in 12 volunteers the time and concentration-dependent effects of sodium hyaluronate on their short precorneal tear film breakup time (BUT, 10 sec. or less) at a low tear volume (15 mm or less by using the phenol red thread test). Each subject underwent four separate study periods, receiving one of the following four ophthalmic solutions during each period: 0.05, 0.1, 0.3% w/v sodium hyaluronate (molecular weight, about 1,000,000) or the vehicle alone. BUT was measured non-invasively using a non-contact specular microscope before and 5, 15, 30, 60, 120, and 180 minutes after drug application. While BUT was not significantly prolonged after instilling either the vehicle or 0.05% solution, it was significantly increased at all times after applying either 0.1% or 0.3% solution, as compared to preinstillation. These results indicate that sodium hyaluronate solutions at concentrations of at least 0.1% can be effective in alleviating symptoms of dry eye.