gebhart/patrepeval huggingface dataset:
Mechanistic Evaluation of the Pros and Cons of Digital RT-LAMP for HIV-1 Viral Load Quantification on a Microfluidic Device and Improved Efficiency via a Two-Step Digital Protocol (2013)

Here we used a SlipChip microfluidic device to evaluate the performance of digital reverse transcription-loop-mediated isothermal amplification (dRT-LAMP) for quantification of HIV viral RNA. Tests are needed for monitoring HIV viral load to control the emergence of drug resistance and to diagnose acute HIV infections. In resource-limited settings, in vitro measurement of HIV viral load in a simple format is especially needed, and single-molecule counting using a digital format could provide a potential solution. We showed here that when one-step dRT-LAMP is used for quantification of HIV RNA, the digital count is lower than expected and is limited by the yield of desired cDNA. We were able to overcome the limitations by developing a microfluidic protocol to manipulate many single molecules in parallel through a two-step digital process. In the first step we compartmentalize the individual RNA molecules (based on Poisson statistics) and perform reverse transcription on each RNA molecule independently to produce DNA. In the second step, we perform the LAMP amplification on all individual DNA molecules in parallel. Using this new protocol, we increased the absolute efficiency (the ratio between the concentration calculated from the actual count and the expected concentration) of dRT-LAMP 10-fold, from ∼2% to ∼23%, by (i) using a more efficient reverse transcriptase, (ii) introducing RNase H to break up the DNA:RNA hybrid, and (iii) adding only the BIP primer during the RT step. We also used this two-step method to quantify HIV RNA purified from four patient samples and found that in some cases, the quantification results were highly sensitive to the sequence of the patient’s HIV RNA. We learned the following three lessons from this work: (i) digital amplification technologies, including dLAMP and dPCR, may give adequate dilution curves and yet have low efficiency, thereby providing quantification values that underestimate the true concentration. Careful validation is essential before a method is considered to provide absolute quantification; (ii) the sensitivity of dLAMP to the sequence of the target nucleic acid necessitates additional validation with patient samples carrying the full spectrum of mutations; (iii) for multistep digital amplification chemistries, such as a combination of reverse transcription with amplification, microfluidic devices may be used to decouple these steps from one another and to perform them under different, individually optimized conditions for improved efficiency.
Small cell lung cancer: Where do we go from here? (2014)

Small cell lung cancer (SCLC) is an aggressive disease that accounts for approximately 14% of all lung cancers. In the United States, approximately 31,000 patients are diagnosed annually with SCLC. Despite numerous clinical trials, including at least 40 phase 3 trials since the 1970s, systemic treatment for patients with SCLC has not changed significantly in the past several decades. Consequently, the 5-year survival rate remains low at <7% overall, and most patients survive for only 1 year or less after diagnosis. Unlike nonsmall cell lung cancer (NSCLC), in which major advances have been made using targeted therapies, there are still no approved targeted drugs for SCLC. Significant barriers to progress in SCLC include 1) a lack of early detection modalities, 2) limited tumor tissue for translational research (eg, molecular profiling of DNA, RNA, and/or protein alterations) because of small diagnostic biopsies and the rare use of surgical resection in standard treatment, and 3) rapid disease progression with poor understanding of the mechanisms contributing to therapeutic resistance. In this report, the authors review the current state of SCLC treatment, recent advances in current understanding of the underlying disease biology, and opportunities to advance translational research and therapeutic approaches for patients with SCLC.
Analysis of kappa light chain contribution to anti-DNA antibody activity of a human VH4-21-encoded monoclonal antibody (NE-1) by antibody-phage display technique. (1998)

Although contribution of light chain to DNA reactivity of some murine anti-DNA antibodies (Abs) has been demonstrated, similar studies on human anti-DNA Abs are limited. To investigate this contribution, we reproduced Fab molecules on the surface of phages from a human B cell line producing IgM anti-DNA monoclonal Ab (NE-1) by an Ab-phage display technique. Expressed Fab molecules (p4-1 clone) were similar to the parental mAb in their binding activities and idiotypic expression. We constructed a light chain shuffled library containing Vkappa genes derived from peripheral blood lymphocytes of a patient with systemic lupus erythematosus (SLE) in combination with the NE-1 heavy chain gene. After panning to ss- or dsDNA, 7 Fab-phage clones which showed significant bindings to ss- or dsDNA were isolated. Many other Fab-phage clones from the library did not bind to ss- nor dsDNA. Sequence analysis revealed that light chains of the 7 clones are derived from diverse Vkappa germline genes including rarely used ones such as the L5 and A30. Most of the Vk germline genes have been used for previously reported anti-DNA antibodies. These findings suggest that diverse Vkappa genes can pair with the NE-1 heavy chain for anti-DNA Ab activity. In addition, kappa light chains seem to modulate DNA binding activities in various ways.
Imaging superficial tissues with polarized light (2000)

The results are consistent with the hypothesis that birefringent tissues randomize linearly polarized light more rapidly than nonbirefringent tissues. The results suggest that polarized light imaging of skin yields images based only on photons backscattered from the superficial epidermal and initial papillary dermis because the birefringent dermal collagen rapidly randomizes polarized light. This anatomic region of the skin is where cancer commonly arises.
The role of costimulation in antibody deficiencies: ICOS and common variable immunodeficiency (2009)

The identification of mutations in the inducible costimulator (ICOS) gene in nine patients with common variable immunodeficiency (CVID) was a major breakthrough. CVID is a complex, highly heterogeneous primary immunodeficiency disease, and the discovery of these mutations revealed a molecular basis. ICOS belongs to the CD28 family of costimulatory molecules and is expressed exclusively on activated T cells. It has at least three critical functions: germinal center formation, isotype class switching, and the development of memory B cells. The discovery of human ICOS deficiency showed that a monogenic disorder could account for the full spectrum of manifestations seen in childhood and adulthood-onset CVID, including autoimmune, inflammatory, and malignant disease complications, as well as recurrent infections. Moreover, this discovery showed that a disorder which had previously been perceived as a B-cell disease might in fact have its genetic origin in human T cells. In this article, we review the role of ICOS in the mammalian immune system and human disease, as well as the discovery and characteristics of patients with ICOS deficiency. Finally, we also discuss how these 'human knockouts' have contributed to our understanding of ICOS functions and have suggested potential avenues for using therapeutic ICOS manipulation to treat other diseases.
A Semi-Synthetic Ion Channel Platform for Detection of Phosphatase and Protease Activity (2009)

Sensitive methods to probe the activity of enzymes are important for clinical assays and for elucidating the role of these proteins in complex biochemical networks. This paper describes a semi-synthetic ion channel platform for detecting the activity of two different classes of enzymes with high sensitivity. In the first case, this method uses single ion channel conductance measurements to follow the enzyme-catalyzed hydrolysis of a phosphate group attached to the C-terminus of gramicidin A (gA, an ion channel-forming peptide) in the presence of alkaline phosphatase (AP). Enzymatic hydrolysis of this phosphate group removes negative charges from the entrance of the gA pore, resulting in a product with measurably reduced single ion channel conductance compared to the original gA-phosphate substrate. This technique employs a standard, commercial bilayer setup and takes advantage of the catalytic turnover of enzymes and the amplification characteristics of ion flux through individual gA pores to detect picomolar concentrations of active AP in solution. Furthermore, this technique makes it possible to study the kinetics of an enzyme and provides an estimate for the observed rate constant (k(cat)) and the Michaelis constant (K(M)) by following the conversion of the gA-phosphate substrate to product over time in the presence of different concentrations of AP. In the second case, modification of gA with a substrate for proteolytic cleavage by anthrax lethal factor (LF) afforded a sensitive method for detection of LF activity, illustrating the utility of ion channel-based sensing for detection of a potential biowarfare agent. This ion channel-based platform represents a powerful, novel approach to monitor the activity of femtomoles to picomoles of two different classes of enzymes in solution. Furthermore, this platform has the potential for realizing miniaturized, cost-effective bioanalytical assays that complement currently established assays.
Event-Driven Data Acquisition and Digital Signal Processing—A Tutorial (2010)

Event-driven analog-to-digital conversion and associated digital signal processing techniques are reviewed. Such techniques, still in the research stage, have the potential to significantly reduce the consumption of energy and bandwidth resources in several important applications.
V H 1-69 gene is preferentially used by hepatitis C virus–associated B cell lymphomas and by normal B cells responding to the E2 viral antigen (2001)

Hepatitis C virus (HCV)-associated B cell lymphomas were previously shown to express a restricted repertoire of immunoglobulin V(H) and V(L) genes, V(H)1-69 and VkappaA27, respectively. Although this suggests a role for antigen selection in the pathogenesis of these lymphomas, the driving antigen involved in the clonal expansion has not been identified. B cell response to a viral antigen, the HCV envelope glycoprotein 2 (E2), was analyzed in an asymptomatic HCV-infected patient. Single B cells, immortalized as hybridomas and selected for binding E2, were analyzed for their V gene usage. Sequences of these V region genes demonstrated that each hybridoma expressed unique V(H) and V(L) genes. Remarkably, these anti-E2 hybridomas preferentially used the V(H)1-69 gene. Analysis of replacement to silent mutation ratios indicated that the genes underwent somatic mutation and antigenic selection. In a separate report, human anti-E2 antibodies were also shown to express the same V(H) gene. These data strengthen the hypothesis that the HCV-associated lymphomas are derived from clonally expanded B cells stimulated by HCV.
El Derecho como alternativa (2009)

Reproducimos a continuacion el texto del discurso pronunciado por el Magistrado Xiol Rios en el acto en el que le fue entregado el Premio Pelayo. La profundidad de sus palabras, la conviccion y autenticidad que destilan y la fuerte conviccion y fe en el Derecho como instrumento de articulacion y convivencia social, asi como en la propia Administracion de Justicia que tan bien conoce el autor, hacen que la lectura de este texto sea un verdadero deleite para cualquier profesional del Derecho y un privilegio su publicacion en nuestro Diario.
A semantic taxonomy-based personalizable meta-search agent (2005)

We address the problem of specifying Web searches and retrieving, filtering and rating Web pages so as to improve the relevance and quality of hits, based on the user's search intent and preferences. We present a methodology and architecture for an agent-based system, called WebSifter II, that captures the semantics of a user's decision-oriented search intent, transforms the semantic query into target queries for existing search engines, and then ranks the resulting page hits according to a user-specified weighted-rating scheme. Users create personalized search taxonomies via our weighted semantic-taxonomy tree. Consulting a Web taxonomy agent such as Wordnet helps refine the terms in the tree. The concepts represented in the tree are then transformed into a collection of queries processed by existing search engines. Each returned page is rated according to user-specified preferences such as semantic relevance, syntactic relevance, categorical match, page popularity and authority/hub rating.
Optimal Design of ORC Systems with a Low-Temperature Heat Source (2012)

A numerical model of subcritical and trans-critical power cycles using a fixed-flowrate low-temperature heat source has been validated and used to calculate the combinations of the maximum cycle pressure (Pev) and the difference between the source temperature and the maximum working fluid temperature (DT) which maximize the thermal efficiency (ηth) or minimize the non-dimensional exergy losses (β), the total thermal conductance of the heat exchangers (UAt) and the turbine size (SP). Optimum combinations of Pev and DT were calculated for each one of these four objective functions for two working fluids (R134a, R141b), three source temperatures and three values of the non-dimensional power output. The ratio of UAt over the net power output (which is a first approximation of the initial cost per kW) shows that R141b is the better working fluid for the conditions under study.
Updates on Managements for Keratoconus (2017)

A commonality of the reviewed papers was the advancement of novel diagnostic and treatment methods in ophthalmology, which can delay the need for corneal grafting. A better understanding of keratoconus treatment options can help enhance visual rehabilitation and prevent blindness in keratoconus patients.
Deficiency of connexin43 gap junctions is an independent marker for breast tumors. (1999)

Gap junctions are intercellular channels that are formed from members of a family of proteins, the connexins (Cxs). Gap junctions play an important role in vital functions, including the regulation of cell growth and cell differentiation. Here, we examined the expression of Cx43, a major Cx in breast tissue, in 32 surgical specimens obtained from breast cancer patients who underwent a primary surgical resection prior to chemotherapy or radiotherapy treatments. The expression of Cx43 gap junctions was compared to the levels of estrogen, progesterone, and erbB2 tyrosine kinase receptors. In addition, a panel of breast cancer cell lines and a series of normal rat mammary tissues and rat mammary tumors induced in vivo by dimethylbenz(a)anthracene were studied. We demonstrated that the lack of Cx43 gap junctions is a common feature of human mammary cancer tissues compared to nonneoplastic breast tissues surrounding primary tumors. Cx43 gap junctions were not observed in ductal carcinomas in situ, infiltrating ductal carcinomas, and infiltrating lobular carcinomas, and they seem to be independent of estrogen, progesterone, and erbB2 receptor status. In breast cancer cell lines and rodent mammary carcinoma tissues, down-regulation of Cx43 occurs at the mRNA level, suggesting a transcriptional mechanism for the decrease of Cx43 protein in breast cancer. In summary, this study provides evidence of decreased expression of Cx43 gap junctions in breast cancer at various stages of progression as well as breast cancer cell lines and raises the possibility that Cx43 may be a useful marker for detecting early oncogenesis in the breast. Because Cx43 gap junctions are lacking in breast cancer and restoration of Cx43 has been shown to reverse the malignant phenotype in vitro, pharmacological up-regulation of Cx43 may prove beneficial in cancer therapeutics.
Kinetics of 2-Methylfuran Acylation with Fatty Acid Anhydrides for Biorenewable Surfactants (2020)

Friedel–Crafts acylation using long-chain fatty acid derivatives and biomass-derived furans is the key reaction to produce “alkyl furan ketones”, an important precursor for biorenewable oleo-furan surfactants. In this work, the steady-state acylation kinetics and reaction mechanism were investigated using a model system of 2-methylfuran and n-octanoic anhydride in a fixed-bed tubular reactor using Al-MCM-41, a mesoporous aluminosilicate. An apparent activation energy (15.5 ± 1.4 kcal mol–1) was obtained for the formation of the acylated product, 2-octanoyl-5-methylfuran (2O5MF), for a temperature range of 348–408 K. The apparent reaction rate orders were ∼0.6 and ∼0.5 in the 2-methylfuran and anhydride concentrations, respectively, while near-zero apparent rate orders were measured in the product concentrations, indicating negligible product inhibition. An Eley–Rideal catalytic acylation mechanism was proposed to explain the experimentally observed apparent rate orders.
Recombinant Adeno-Associated Viral Vector Production and Purification (2011)

Gene delivery vectors based on recombinant adeno-associated virus (AAV) are powerful tools for studying myogenesis in normal and diseased conditions. Strategies have been developed to use AAV to increase, down-regulate, or modify expression of a particular muscle gene in a specific muscle, muscle group(s), or all muscles in the body. AAV-based muscle gene therapy has been shown to cure several inherited muscle diseases in animal models. Early clinical trials have also yielded promising results. In general, AAV vectors lead to robust, long-term in vivo transduction in rodents, dogs, and non-human primates. To meet specific research needs, investigators have developed numerous AAV variants by engineering viral capsid and/or genome. Here we outline a generic AAV production and purification protocol. Techniques described here are applicable to any AAV variant.
Geocasting with guaranteed delivery in sensor networks (2004)

In a geocasting problem, a message is sent from one node to all the nodes located in a designated region. For example, a monitoring center needs to contact all active sensors within a monitored area to either gather data from them periodically or provide its location to sensors covering a certain area for event reporting. Intelligent flooding methods exist for this task when all active sensors belong to the monitored area. However, when a particular area containing only a small subset of active sensors needs to be monitored, the problem reduces to geocasting. Most existing geocasting solutions are shown not to guarantee delivery. We describe three approaches to guarantee delivery. Two of them are face traversal schemes, based on depth-first search of the face tree and traversal of all faces that intersect the border of the geocasting region, respectively. In the entrance zone multicasting-based approach, the monitoring center divides the entrance ring of a geocast region into zones of diameter equal to the transmission radius. The problem is decomposed into multicasting toward the center of each zone, and flooding from these nodes. Improvements to all methods can be made by applying neighbor or area dominating sets and coverage, and converting nodes that are not selected to sleep mode. All solutions that guarantee delivery are reported here for the first time (except a message inefficient version of the face tree traversal scheme).
Stereoselective total synthesis of the complement inhibitor K-76 (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective total synthesis of the complement inhibitor K-76John E. McMurry and Mark D. ErionCite this: J. Am. Chem. Soc. 1985, 107, 9, 2712–2720Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/ja00295a025https://doi.org/10.1021/ja00295a025research-articleACS PublicationsRequest reuse permissionsArticle Views1992Altmetric-Citations90LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The role of melatonin in immuno‐enhancement: potential application in cancer (2006)

Melatonin, a neurohormone produced mainly by the pineal gland, is a modulator of haemopoiesis and of immune cell production and function, both in vivo and in vitro. Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines, and its administration favours Th1 priming. In both normal and leukaemic mice, melatonin administration results in quantitative and functional enhancement of natural killer (NK) cells, whose role is to mediate defenses against virus-infected and cancer cells. Melatonin appears to regulate cell dynamics, including the proliferative and maturational stages of virtually all haemopoietic and immune cells lineages involved in host defense - not only NK cells but also T and B lymphocytes, granulocytes and monocytes - in both bone marrow and tissues. In particular, melatonin is a powerful antiapoptotic signal promoting the survival of normal granulocytes and B lymphocytes. In mice bearing mid-stage leukaemia, daily administration of melatonin results in a survival index of 30-40% vs. 0% in untreated mice. Thus, melatonin seems to have a fundamental role as a system regulator in haemopoiesis and immuno-enhancement, appears to be closely involved in several fundamental aspects of host defense and has the potential to be useful as an adjuvant tumour immunotherapeutic agent.