gebhart/patrepeval huggingface dataset:
Integrin signaling: roles for the cytoplasmic tails of αIIbβ3 in the tyrosine phosphorylation of pp125FAK (1995)

pp125FAK (focal adhesion kinase) a protein tyrosine kinase that may mediate cellular responses to adhesion, is activated and tyrosine-phosphorylated when platelets adhere to fibrinogen via the integrin, alpha IIb beta 3. To determine whether either of the cytoplasmic tails of alpha IIb beta 3 regulates FAK phosphorylation, CHO cells were stably transfected with alpha IIb beta 3 or various cytoplasmic tail truncation mutants. Cells expressing wild-type alpha IIb beta 3 or alpha IIb beta 3 that lacked the COOH-terminal 13 or 18 residues of the 20 residue alpha IIb tail adhered to and spread on fibrinogen or on an anti-alpha IIb antibody, and FAK became tyrosine-phosphorylated. FAK also became phosphorylated in adherent cells lacking the COOH-terminal 35 or 39 residues of the 47 residue beta 3 tail, although the extent of phosphorylation was reduced by about 50% in the latter mutant. Little or no FAK phosphorylation was observed if 46 residues were deleted from the beta 3 tail. None of these beta 3 truncation mutants spread on the anti-alpha IIb antibody. When cells with wild-type alpha IIb beta 3 or truncated beta 3 were detached from a surface, FAK became rapidly dephosphorylated. In contrast, FAK remained phosphorylated in the two alpha IIb truncation mutants for up to 90 minutes in suspension. This persistent phosphorylation was not due to occupancy of alpha IIb beta 3 by adhesive ligands because it was also observed with an alpha IIb tail truncation mutant that contained an additional mutation in the extracellular portion of the receptor that prevents ligand binding. These studies demonstrate that: (1) the beta 3 cytoplasmic tail, including the membrane-proximal portion, is involved in initiation of FAK phosphorylation; (2) FAK phosphorylation can be initiated by cell adhesion in the absence of cell spreading; and (3) the membrane-distal portion of the alpha IIb cytoplasmic tail may normally function to dampen FAK phosphorylation in non-anchored cells.
Database resources of the National Center for Biotechnology Information (2017)

The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. The Entrez system provides search and retrieval operations for most of these data from 39 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. New resources released in the past year include PubMed Data Management, RefSeq Functional Elements, genome data download, variation services API, Magic-BLAST, QuickBLASTp, and Identical Protein Groups. Resources that were updated in the past year include the genome data viewer, a human genome resources page, Gene, virus variation, OSIRIS, and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
Design and Optimization of Molecular Beacon Real-Time Polymerase Chain Reaction Assays (2004)

During the last few years, several innovative technologies have become available for performing sensitive and accurate genetic analyses. These techniques use fluorescent detection strategies in combination with nucleic acid amplification protocols. Most commonly used is the real-time polymerase chain reaction (PCR). To achieve the maximum potential of a real-time PCR assay, several parameters must be evaluated and optimized independently. This chapter describes the different steps necessary for establishing a molecular beacon real-time PCR assay: (1) target design, (2) primer design, (3) optimization of the amplification reaction conditions using SYBR Green, (4) molecular beacon design, and (5) molecular beacon synthesis and characterization. The last section provides an example of a multiplex quantitative real-time PCR.
Impairment of Antigen-Presenting Cell Function in Mice Lacking Expression of Ox40 Ligand (2000)

OX40 expressed on activated T cells is known to be an important costimulatory molecule on T cell activation in vitro. However, the in vivo functional significance of the interaction between OX40 and its ligand, OX40L, is still unclear. To investigate the role of OX40L during in vivo immune responses, we generated OX40L-deficient mice and a blocking anti-OX40L monoclonal antibody, MGP34. OX40L expression was demonstrated on splenic B cells after CD40 and anti-immunoglobulin (Ig)M stimulation, while only CD40 ligation was capable of inducing OX40L on dendritic cells. OX40L-deficient and MGP34-treated mice engendered apparent suppression of the recall reaction of T cells primed with both protein antigens and alloantigens and a significant reduction in keyhole limpet hemocyanin-specific IgG production. The impaired T cell priming was also accompanied by a concomitant reduction of both T helper type 1 (Th1) and Th2 cytokines. Furthermore, antigen-presenting cells (APCs) derived from the mutant mice revealed an impaired intrinsic APC function, demonstrating the importance of OX40L in both the priming and effector phases of T cell activation. Collectively, these results provide convincing evidence that OX40L, expressed on APCs, plays a critical role in antigen-specific T cell responses in vivo.
Timing the Application of Security Patches for Optimal Uptime (2002)

Security vulnerabilities are discovered, become publicly known, get exploited by attackers, and patches come out. When should one apply security patches? Patch too soon, and you may suffer from instability induced by bugs in the patches. Patch too late, and you get hacked by attackers exploiting the vulnerability.Weexplore the factors affecting when it is best to apply security patches, providing both mathematical models of the factors affecting when to patch, and collecting empirical data to give the model practical value. Weconclude with a model that we hope will help provide a formal foundation for when the practitioner should apply security updates.
Key Principles and Clinical Applications of “Next-Generation” DNA Sequencing (2012)

Demand for fast, inexpensive, and accurate DNA sequencing data has led to the birth and dominance of a new generation of sequencing technologies. So-called "next-generation" sequencing technologies enable rapid generation of data by sequencing massive amounts of DNA in parallel using diverse methodologies which overcome the limitations of Sanger sequencing methods used to sequence the first human genome. Despite opening new frontiers of genomics research, the fundamental shift away from the Sanger sequencing that next-generation technologies has created has also left many unaware of the capabilities and applications of these new technologies, especially those in the clinical realm. Moreover, the brisk evolution of sequencing technologies has flooded the market with commercially available sequencing platforms, whose unique chemistries and diverse applications stand as another obstacle restricting the potential of next-generation sequencing. This review serves to provide a primer on next-generation sequencing technologies for clinical researchers and physician scientists. We provide an overview of the capabilities and clinical applications of DNA sequencing technologies to raise awareness among researchers about the power of these novel genomic tools. In addition, we discuss that key sequencing principles provide a comparison between existing and near-term technologies and outline key advantages and disadvantages between different sequencing platforms to help researchers choose an appropriate platform for their research interests.
Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. (2003)

Abeta was present in 4 of 9 AMD eyes. Within these eyes, Abeta localized to a subset of drusen. None of the 9 normal eyes surveyed, some of which had small drusen, were A beta positive. Abetapositive vesicles were most numerous in GA eyes at the edges of atrophy, the region at risk for further degeneration. These results suggest that Abeta in drusen correlates with the location of degenerating photoreceptors and retinal pigment epithelium (RPE) cells. Further work will be necessary to determine whether Abeta deposition in drusen may contribute to or result from retinal degeneration.
Production of γ-Linolenic Acid and Stearidonic Acid in Seeds of Marker-Free Transgenic Soybean (2004)

Through a single desaturation step, the Borago officinalis L. Δ6 desaturase can convert linoleic acid and α-linolenic acid to γ-linolenic acid (GLA) and stearidonic acid (STA), respectively. Both GLA and STA are of interest to the pharmaceutical and nutraceutical industries. Production of these fatty acids is costly. One potential strategy to reduce production cost would be to generate them in a major oilseed crop. To this end, a cDNA of the B. officinalis Δ6-desaturase gene was cloned downstream of the embryo-specific promoter β-conglycinin. The resultant cassette was assembled into a two T-DNA binary vector, in which the second T-DNA element harbored a selectable marker cassette. The final plasmid was subsequently used to transform soybean [Glycine max (L.) Merr.]. The simultaneous delivery of two T-DNA elements was used as a strategy to derive soybean progeny transgenic for the Δ6 desaturase T-DNA and free of the marker gene T-DNA. Twenty-nine transgenic soybean lines were recovered that harbored both T-DNA elements, of which 17 produced GLA and STA in the seed storage lipids. Average GLA levels ranged from 3.4 up to 28.7%, while STA levels varied from just under 0.6 to 4.2% in the T1 generation. Among the 17 lines that produced GLA and STA, four lines were identified that were free of the selectable marker T-DNA element.
Emigración gallega y esclavitud en Cuba (1854). Un problema de estado. (2000)

1. La institucion de la esclavitud esta presente en las colonias espanolas desde el momento inmediatamente posterior a los descubrimientos del nuevo mundo. El mantenimiento de esclavos habia sido practica incuestionada tanto por quienes se beneficiaban del trabajo de los esclavos como por las autoridades politicas y religiosas. Sin embargo, a finales del siglo XVIII en Cuba la institucion de la esclavitud experimento un profundo cambio; aumento la demanda interna de esclavos, cambiaron las condiciones de trabajo y la vida impuestas a ellos. Se genero, ademas, un trafico de hombres y mujeres de color que proporciono grandes beneficios, pero a la vez modificaron la vida en toda la isla. Los cambios estructurales experimentados en los estados europeos a principios del siglo XIX hicieron insostenible el mantenimiento discursivo de la institucion de la esclavitud, lo que unido al proceso de emancipacion de las colonias del Caribe, contribuyo a que la abolieran Gran Bretana, Francia y Holanda. Por razones de estado el trabajo esclavo paso a llamarse asalariado y quienes lo realizaban pasaron a ser ciudadanos, categoria acorde con el discurso politico y juridico moderno. Sin embargo, en la colonia espanola, el mantenimiento de la esclavitud se manifesto un fenomeno economico imprescindible y condiciono las relaciones de esta con la metropoli hasta el momento mismo en que Cuba consiguio la independencia.
Base- and Ligand-free Room-Temperature Synthesis of N-Fused Heteroaromatic Compounds via the Transition Metal-Catalyzed Cycloisomerization Protocol (2007)

A new practical method for the synthesis of N-fused heterocycles via the transition metal-catalyzed cycloisomerization of heterocyles possessing a propagyl group has been developed. This very mild, base- and ligand-free method allows for the synthesis of diverse fused heterocyclic cores in good to excellent yields.
Drug Dosage for Infants and Children (1965)

Dosage is the heart of drug therapy. It is therapy in action. Right or wrong, it is the final expression of diagnostic and therapeutic acumen. Many factors, including absorption, distribution, storage, degradation, conjugation, and excretion, contribute to correct dosage, and marked differences in these factors exist in the various age groups. Yet, for many years, children's dosages have, for the most part, been poorly derived as fractions of adult doses. Ideally, the best dose is the minimal quantity that produces the desired effect without causing adverse reactions. Unfortunately, adverse reactions are an inevitable part of the total effect of a drug; however, they can be minimized by correct dosage. <i>The United States Pharmacopeia</i><sup>1</sup>and the<i>National Formulary</i><sup>2</sup>define the<i>usual dose</i>as "that which may be expected ordinarily to produce in adults, following oral administration at such time intervals as may be specified, the therapeutic effect for which the
Implementation of STARNET: a WDM computer communications network (1996)

STARNET is a broadband backbone optical wavelength-division multiplexing (WDM) local area network (LAN). Based on a physical passive star topology, STARNET offers all users two logical subnetworks: a high-speed reconfigurable packet-switched data subnetwork and a moderate-speed fix-tuned packet-switched control subnetwork. Thus, STARNET supports traffic with a wide range of speed and continuity characteristics. We report the analysis and implementation of an entire STARNET two-node network, from the optical to the computer layer, at the Optical Communications Research Laboratory (OCRL) of Stanford University. To implement the two logical subnetworks, we designed and implemented two different techniques: combined modulation and multichannel subcarrier multiplexing (MSCM). OCRL has already demonstrated several combined modulation techniques such as phase shift-keyed and amplitude shift-keyed (PSK/ASK), and differential phase shift-keyed and amplitude shift-keyed (DPSK/ASK), yielding combined ASK/DPSK modulation receiver sensitivities better than -32 dBm. OCRL has designed and implemented a high-speed high-performance packet-switched STARNET computer interface which enables high-throughput transfer to/from host computer, low latency switching, traffic prioritization, and capability of multicasting and broadcasting. With this interface board, OCRL has achieved average transmit and receive throughputs of 685 Mb/s and 571 Mb/s, respectively, out of the 800 Mb/s theoretical maximum of the host computer bus. The incurred packet latency due to the interface for a specified multihop network configuration has been simulated to be 24 /spl mu/s. Using simulation and experimental results, it is shown that STARNET is highly suitable for high-speed multimedia network applications.
Validity of maternal reporting of breast feeding history and the association with blood lipids in 17 year olds in Jerusalem. (1984)

The validity of mothers' reporting of the breast feeding history of their children more than 20 years after their birth was studied in a Jerusalem population. Among 74 study subjects, duration of breast feeding as ascertained from an interview was well correlated with that recorded in mother and child health clinic charts. Concordance was of similar magnitude in subgroups of ethnicity, mother's education, family size, and sex of child. Duration of breast feeding in 101 youngsters was inversely associated with plasma cholesterol in 17 year old girls, though not in boys, which was statistically significant on univariate analysis and of borderline significance on multivariable analysis. Among 17 year old boys, though not in girls, a statistically significant inverse association for plasma triglyceride was apparent on multivariable analysis. Reported breast feeding history derived from interview of mothers may be a useful instrument for study of possible long term effects of breast feeding in their adolescent or adult progeny.
Circulating interleukin-1β and tumor necrosis factor-α concentrations after burn injury in humans (1992)

These results indicate that early after burn injury there is a correspondence of IL-1 beta and TNF alpha with certain host responses, but these correlations disappear with the progression of illness. In general, IL-1 beta and TNF alpha appear to be poor indicators of prognosis during burn injury; however, the association of mortality with low circulating IL-1 beta values supports the concept of IL-1 beta as being an essential mediator of host defenses.
A conditionally replicative adenovirus that codes for a TK-GFP fusion protein (Ad5Δ24TK-GFP) for evaluation of the potency of oncolytic virotherapy combined with molecular chemotherapy (2006)

The utility of conditionally replicative adenoviruses (CRAds) in cancer gene therapy is based on their ability to destroy tumor cells by oncolysis. However, in order to achieve adequate therapeutic response, CRAds have to spread through the tumor tissue by replication. Thus, to study the potency of these viruses to replicate and penetrate in tumors, we created a herpes simplex virus type 1 thymidine kinase-green fluorescent protein fusion gene (TK-GFP) encompassing CRAd (Ad5Delta24TK-GFP), whose tumor selectivity is mediated by a retinoblastoma (Rb)-binding site mutation. In addition, we evaluated the oncolytic efficacy of Ad5Delta24TK-GFP in combination with the TK/ganciclovir (GCV) system. Based on our results, Ad5Delta24TK-GFP replicates in cancer cells resulting in oncolysis and can efficiently penetrate into tumors. Additionally, the combination of GCV with Ad5Delta24TK-GFP augmented cell death in vitro but this was not observed in vivo: tumor growth was significantly reduced by oncolysis when compared to non-replicative virus (p<0.001), but administration of GCV did not significantly enhance oncolysis. This suggests that in certain conditions, TK/GCV-mediated cell killing may be counterproductive to replication and oncolysis, which on the other hand might be useful feature for clinical trials in case of replication-associated toxicity.
Markers of Increased Risk of Intracerebral Hemorrhage After Intravenous Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke in Clinical Practice (2002)

Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH. These factors require confirmation in a prospective cohort before clinical implementation.
Effect of Diabetes in the BB Wistar Rat on the Peptidergic Component of the Enteric Innervation (1990)

Whole mount preparations of the small intestine from Wistar, normoglycemic 90-day diabetic BB, hyperglycemic 90-day diabetic BB and age-matched nondiabetic BB rats were immunostained to determine the extent of the peptidergic innervation. The neuropeptides examined were vasoactive intestinal peptide, neuropeptide Y, substance P. calcitonin gene-related peptide, galanin and somatostatin. The extent of the peptidergic innervation in the submucous and myenteric plexuses from the control Wistar, nondiabetic BB and normoglycemic diabetic BB rats was identical. In the submucous plexus of the hyperglycemic diabetic BB rats there was a marked reduction in the number of somatostatin-immunoreactive neurons and nerve fibres. Substance P and calcitonin gene-related peptide which are colocalized in a proportion of the somatostatin neurons were unaffected. In the myenteric plexus of the hyperglycemic diabetic BB rats the number and intensity of staining of the galanin-immunoreactive nerve fibers was markedly increased. Galanin has not been observed to colocalize with any of the other neuropeptides examined.
Bordetella pertussis adenylate cyclase. Purification, characterization, and radioimmunoassay. (1986)

The extracellular adenylate cyclase of Bordetella pertussis was purified either as a free enzyme or as a complex with calmodulin. The purified enzyme has a specific activity of 1600 mumol of cAMP min-1 X mg-1 and exists under two molecular forms of 45 and 43 kDa which are apparently structurally related. Calmodulin increased considerably the resistance of adenylate cyclase to inactivation by trypsin. Although trypsin cleaved the adenylate cyclase-calmodulin complex, the digested fragments remained associated by noncovalent interactions in an active conformation. Specific mouse anti-adenylate cyclase antibodies inhibit adenylate cyclase activity and were used to develop a specific radioimmunoassay that allows detection of as little as 5 ng of adenylate cyclase in culture supernatants.
Biped walking on a low friction floor (2005)

Biped walking on a low friction floor is analyzed in this paper. For a given walking pattern, we can calculate a necessary friction coefficient which allows the robot to perform the expected motion. To reduce the maximum necessary friction coefficient, a pattern generation based on preview control theory is explained. We also describe a calculation of slip concerned ZMP, which provides a good prediction of falling caused by slips. Finally, we test a walk of 135 [km/h] on low friction environment using a humanoid robot HRP-2. The robot could successfully walk over the slippery area whose friction coefficient is 0.14.
MRI Contrast Agents: Current Status and Future Perspectives (2007)

Magnetic Resonance Imaging (MRI) is increasingly used in clinical diagnostics, for a rapidly growing number of indications. The MRI technique is non-invasive and can provide information on the anatomy, function and metabolism of tissues in vivo. MRI scans of tissue anatomy and function make use of the two hydrogen atoms in water to generate the image. Apart from differences in the local water content, the basic contrast in the MR image mainly results from regional differences in the intrinsic relaxation times T(1) and T(2), each of which can be independently chosen to dominate image contrast. However, the intrinsic contrast provided by the water T(1) and T(2) and changes in their values brought about by tissue pathology are often too limited to enable a sensitive and specific diagnosis. For that reason increasing use is made of MRI contrast agents that alter the image contrast following intravenous injection. The degree and location of the contrast changes provide substantial diagnostic information. Certain contrast agents are predominantly used to shorten the T(1) relaxation time and these are mainly based on low-molecular weight chelates of the gadolinium ion (Gd(3+)). The most widely used T(2) shortening agents are based on iron oxide (FeO) particles. Depending on their chemical composition, molecular structure and overall size, the in vivo distribution volume and pharmacokinetic properties vary widely between different contrast agents and these largely determine their use in specific diagnostic tests. This review describes the current status, as well as recent and future developments of MRI contrast agents with focus on applications in oncology. First the basis of MR image contrast and how it is altered by contrast agents will be discussed. After some considerations on bioavailability and pharmacokinetics, specific applications of contrast agents will be presented according to their specific purposes, starting with non-specific contrast agents used in classical contrast enhanced magnetic resonance angiography (MRA) and dynamic contrast enhanced MRI. Next targeted contrast agents, which are actively directed towards a specific molecular target using an appropriate ligand, functional contrast agents, mainly used for functional brain and heart imaging, smart contrast agents, which generate contrast as a response to a change in their physical environment as a consequence of some biological process, and finally cell labeling agents will be presented. To conclude some future perspectives are discussed.