gebhart/patrepeval huggingface dataset:
Monoclonal antibodies — a proven and rapidly expanding therapeutic modality for human diseases (2010)

The study of antibodies has been a focal point in modern biology and medicine since the early 1900s. However, progress in therapeutic antibody development was slow and intermittent until recently. The first antibody therapy, murine-derived murononab OKT3 for acute organ rejection, was approved by the US Food and Drug Administration (FDA) in 1986, more than a decade after César Milstein and Georges Köhler developed methods for the isolation of mouse monoclonal antibodies from hybridoma cells in 1975. As a result of the scientific, technological, and clinical breakthroughs in the 1980s and 1990s, the pace of therapeutic antibody discovery and development accelerated. Antibodies are becoming a major drug modality with more than two dozen therapeutic antibodies in the clinic and hundreds more in development. Despite the progress, need for improvement exists at every level. Antibody therapeutics provides fertile ground for protein scientists to fulfill the dream of personalized medicine through basic scientific discovery and technological innovation.
A physiological barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery. (1999)

BACKGROUND AND PURPOSE: Osmotic disruption of the blood-brain barrier (BBB) provides a method for transvascular delivery of therapeutic agents to the brain. The apparent global delivery of viral-sized iron oxide particles to the rat brain after BBB opening as seen on MR images was compared with the cellular and subcellular location and distribution of the particles. METHODS: Two dextran-coated superparamagnetic monocrystalline iron oxide nanoparticle contrast agents, MION and Feridex, were administered intraarterially in rats at 10 mg Fe/kg immediately after osmotic opening of the BBB with hyperosmolar mannitol. After 2 to 24 hours, iron distribution in the brain was evaluated first with MR imaging then by histochemical analysis and electron microscopy to assess perivascular and intracellular distribution. RESULTS: After BBB opening, MR images showed enhancement throughout the disrupted hemisphere for both Feridex and MION. Feridex histochemical staining was found in capillaries of the disrupted hemisphere. Electron microscopy showed that the Feridex particles passed the capillary endothelial cells but did not cross beyond the basement membrane. In contrast, after MION delivery, iron histochemistry was detected within cell bodies in the disrupted hemisphere, and the electron-dense MION core was detected intracellularly and extracellularly in the neuropil. CONCLUSION: MR images showing homogeneous delivery to the brain at the macroscopic level did not indicate delivery at the microscopic level. These data support the presence of a physiological barrier at the basal lamina, analogous to the podocyte in the kidney, distal to the anatomic (tight junction) BBB, which may limit the distribution of some proteins and viral particles after transvascular delivery to the brain.
Thermophilic sulfate-reducing bacteria in cold marine sediment (1994)

Sulfate reduction was measured with the 35SO42 -tracer technique in slurries of sediment from Aarhus Bay, Denmark, where seasonal temperatures range from 0 to 15C.The incubations were made at temperatures from 0C to 80C in temperature increments of 2C to search for presence of psychrophilic, mesophilic and thermophilic sulfate-reducing bacteria.Detectable activity was initially only in the mesophilic range, but after a lag phase sulfate reduction by thermophilic sulfate-reducing bacteria were observed.No distinct activity of psychrophilic sulfate-reducing bacteria was detected.Time course experiments showed constant sulfate reduction rates at 4C and 30C, whereas the activity at 60C increased exponentially after a lag period of one day.Thermophilic, endospore-forming sulfate-reducing bacteria, designated strain P60, were isolated and characterized as Desulfotomaculum kuznetsovii.The temperature response of growth and respiration of strain P60 agreed well with the measured sulfate reduction at 50-70C.Bacteria similar to strain P60 could thus be responsible for the measured thermophilic activity.The viable population of thermophilic sulfate-reducing bacteria and the density of their spores was determined in most probable number (MPN) dilutions.The density was 2.8-104 cells'g-1 fresh sediment, and the enumerations suggested that they were all present as spores.This result agrees well with the observed lag period in sulfate reduction above 50C.No environment with temperatures supporting the growth of these thermophiles is known in the region around Aarhus Bay.
The Preparation of Long Chain N-Acylamino Acids (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation of Long Chain N-Acylamino AcidsE. Jungermann, J. F. Gerecht, and I. J. KremsCite this: J. Am. Chem. Soc. 1956, 78, 1, 172–174Publication Date (Print):January 1, 1956Publication History Published online1 May 2002Published inissue 1 January 1956https://pubs.acs.org/doi/10.1021/ja01582a049https://doi.org/10.1021/ja01582a049research-articleACS PublicationsRequest reuse permissionsArticle Views893Altmetric-Citations71LEARN 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 Uncertain Road to Environmental Policy (1995)

There are many circumstances where there is a recognised environmental problem and, although there appears to be support for protection, in practice little is done about it. Policy-making is a complex and uncertain process. Under democratic systems, policies are introduced by governments where they command sufficient political support. The development of policy in response to a new concern for the environment therefore depends first on people appreciating the nature and significance of the problem. Support for action to be taken will depend on a sufficiently widely held recognition that there is a net gain to be had from it and, at least on the part of those who may be negatively affected by a policy, a certain willingness to bear the costs. In many cases it is necessary to mobilise support for action amongst many different countries. In this chapter we will outline some of the characteristics of environmental problems and of the policy decision-making process which can stand in the way of the development of what might appear to be rational environmental policy.
Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha. (1990)

We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3.4 kb and 1.6 kb were easily detected at 2.5 hr of culture and remained stable until 18 hr. In MDP-treated monocytes, three IL-6 RNA species displayed different kinetics of accumulation: a 3.4 kb RNA whose expression already reached its maximum after 2.5 hr exposure to MDP; a 1.6 kb RNA whose expression peaked at 5 hr; and a new RNA species of 1.4 kb which was transiently induced in early time of cell stimulation. TNF-alpha co-operated with MDP to increase IL-6 gene expression and secretion of biological active protein (measured by the hybridoma plasmacytoma growth factor assay). MDP exhibits a broad spectrum of immunomodulation properties such as adjuvant activity, enhancement of macrophage cytotoxicity against tumour and induction of non-specific resistance to intracellular agents. The results reported here suggest that these properties might be linked to the stimulation by MDP of genes coding for key cytokines such as IL-6, TNF and IL-1.
Vector quantiser of video signals (1982)

An efficient design method is presented for a vector quantiser of 16-dimensional vectors based on a long training sequence of normalised video signals. The basic properties are demonstrated by examples.
XQSE: An XQuery Scripting Extension for the AquaLogic Data Services Platform (2008)

The AquaLogic Data Services Platform (ALDSP) is a BEA middleware platform for creating services that access and manipulate information drawn from multiple heterogeneous sources of data. The integration logic for read services is specified declaratively using the XQuery language. ALDSP 3.0, available in December 2007, includes a new XQuery-based Scripting Extension - XQSE - that enables developers to write procedural as well as declarative logic without leaving the XQuery world. In this paper, we describe the XQSE extensions to XQuery and show how they help to support important new classes of data services in ALDSP 3.0.
Intrauterine infections and birth defects. (2004)

Intrauterine infection is an important cause of some birth defects worldwide. The most common pathogens include rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. General information about these pathogens in epidemiology, consequence of birth defects, and the possible mechanisms in the progress of birth defects, and the interventions to prevent or treat these pathogens' infections are described. The infections caused by rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. are common, yet they are proved to be fatal during the pregnant period, especially during the first trimester. These infections may cause sterility, abortion, stillbirth, low birth weight, and affect multiple organs that may induce loss of hearing and vision, even fetal deformity and the long-term effects. These pathogens' infections may influence the microenvironment of placenta, including levels of enzymes and cytokines, and affect chondriosome that may induce the progress of birth defect. Early diagnosis of infections during pregnancy should be strengthened. There are still many things to be settled, such as the molecular mechanisms of birth defects, the effective vaccines to certain pathogens. Birth defect researches in terms of etiology and the development of applicable and sensitive pathogen detection technology and methods are imperative.
Reduction of aberrant crypt formation in the colon of CF1 mice by potential chemopreventive agents (1991)

Carcinogen-induced aberrant crypts (AC) of the colon are a precancerous state that leads to malignancy. The inhibition of AC formation by chemopreventive agents was evaluated in this study. Colon AC were induced by 1,2-dimethylhydrazine (DMH) in 3 weeks in CF1 mice. The cecum of the large intestine of CF1 mice did not produce more than one AC focus per animal. The effect of DMH and that of the inhibitors in this part of the large bowel were essentially similar to the vehicle control and inhibitor-only controls. The response of DMH treatment in the colorectal portion of the large bowel was found to be different from that of the cecum. The DMH treated mice had 13-17 foci per animal in three different experiments. The average number of AC per focus was greater than one in all three experiments performed. None of the inhibitor-only control animals nor the cottonseed oil vehicle control animals developed AC focus in the colorectal or the cecal part of the large bowel. The known inhibitor of colon carcinogenesis 3-butyl-4-hydroxyanisole reduced DMH-induced average AC formation by 10 and 46% at 1 and 4 mg per dose, respectively. The inhibitors 2-n-butylthiophene and phenylpropylisothiocyanate reduced DMH-induced average AC formation greater than 34 and greater than 40% respectively. The postulated inhibitor 2-n-octylthiophene, which is an eight-carbon homolog of 2-n-butylthiophene, similarly reduced DMH-induced AC formation. The known colon carcinogenesis inhibitor dehydroepiandrosterone, in contrast, has no effect. The inactivity of dehydroepiandrosterone to inhibit colon AC formation was attributed to its mechanism of inhibitory action, which differs from that of the phenol, isothiocyanate and thiophenes. The short duration that is required to produce quantifiable results suggests that the reduction of carcinogen-induced AC formation may be developed into a useful prescreening assay for potential chemopreventive agents against colon cancer.
Robust spatial LSB watermarking of color images against JPEG compression (2012)

Digital Watermarking is a technique to embed additional data in digital images, without affecting the original image quality. It has become a useful tool for copyright protection, content authentication and steganography. Least Significant Bit is a commonly used technique in digital image watermarking. It is straight forward to understand and implement, and is widely used in many watermarking algorithms. A common problem of spatial LSB implementation is that a usual image compression can render watermark useless. In this paper we propose an alternative watermarking technique based on spatial LSB modification. It is robust against moderate JPEG compression, while keeping all the features of LSB.
Mediator Tail Module Is Required for Tac1-Activated <i>CDR1</i> Expression and Azole Resistance in Candida albicans (2017)

The human fungal pathogen <i>Candida albicans</i> develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1 and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which <i>C. albicans</i> acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C terminus of Tac1. GOF mutations within the Tac1 TAD, outside the context of full-length Tac1, generally do not enhance its absolute potential as a transcriptional activator. Negative regulation of the Tac1 TAD by the Tac1 middle region is necessary for the activating effect of GOF mutations or fluphenazine to be realized. We have found that full-length Tac1, when hyperactivated by xenobiotics or GOF mutations, facilitates the recruitment of the Mediator coactivator complex to the <i>CDR1</i> promoter. Azole resistance and the activation of Tac1 target genes, such as <i>CDR1</i>, are dependent on the Tac1 TAD and subunits of the Mediator tail module. The dependence of different Tac1 target promoters on the Mediator tail module, however, varies widely. Lastly, we show that hyperactivation of Tac1 is correlated with its Mediator-dependent phosphorylation, a potentially useful biomarker for Tac1 hyperactivation. The role of Mediator in events downstream of Tac1 hyperactivation in fluconazole-resistant clinical isolates is complex and provides opportunities and challenges for therapeutic intervention.
A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity (2021)

T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins<sup>1,2</sup>, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18-80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4<sup>+</sup> and CD8<sup>+</sup> T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.
5-Aryl-3-azabicyclo[3.2.0]heptan-5-one ketals, compounds with morphine-like analgesic activity (1984)

A series of 5-aryl-3-azabicyclo[3.2.0] heptan -6-one ketals 6 were synthesized by hydride reduction of 1-aryl-4, 4-dimethoxy-1,2- cyclobutanedicarboximides 5. Imides 5 were obtained as the sole, regioselective products of the [2 + 2] photocycloaddition of 1,1- dimethoxyethylene to 2- arylmaleimides . The m-methoxyphenyl-N-methyl analogue 6a was demethylated to phenol 7 with EtSNa -DMF. Both 6a and 7 were similar to morphine in analgesic potency in rats and mice and showed physiological effects that were identical with those of morphine and that were completely reversed by naloxone. Compound 7 was identical with morphine in its ability to displace [3H]naloxone from homogenates of rat brain minus cerebellum. A molecular mechanics analysis of the m-methoxyphenyl analogue 6a showed that the nitrogen atom, the methoxyphenyl group, and the methoxyl oxygen cis to the phenyl group can be superimposed on the corresponding features of the morphine molecule, and perhaps this accounts for the observed opiate-receptor binding properties of 7.
PMU based generator parameter identification to improve the system planning and operation (2012)

To ensure the system stability, generator owners are required to provide their generator models and parameters to ISO/RTO for system analysis. In addition to field testing, there is increasing demand of online approach for parameter identification. The approach of Phasor Measurement Unit (PMU) based generator unit's parameter identification is a new emerging technology to satisfy these requirements. However, for large and complex electrical systems, the estimation of generator parameters based on PMU measurements remains a very challenge task. This paper proposed a systematic identification process to provide solution for the parameter identification problems. Three crucial steps are introduced in the proposed process. Firstly, hybrid dynamic simulation is implemented to obtain the dynamic equivalent circuit of the external system to reduce the computational time. Secondly, trajectory sensitivities and parameter correlation analysis is used to determine key parameters to further improve the computational efficiency. Finally, a minimum variance calibration strategy is proposed to derive the parameters of generator. A sample system is used to illustrate the effectiveness of the proposed approach.
Complex glycerol kinase deficiency: A contiguous gene syndrome involving the Duchenne muscular dystrophy, glycerol kinase, and adrenal hypoplasia congenita loci (1996)

Complex glycerol kinase deficiency is a contiguous gene syndrome that involves deletion of the glycerol kinase (GK) gene along with the loci for Duchenne muscular dystrophy (DMD) and/or adrenal hypoplasia congenita (AHC). The deletion breakpoints in these patients allowed identification of the critical regions for the GK and AHC genes, and both were identified using a positional cloning strategy. In addition to complex glycerol kinase deficiency, there are also two distinct phenotypes characterizing isolated glycerol kinase deficiency, the juvenile and benign forms. The juvenile form has onset in the first weeks to years of life with episodic decompensation. These episodes can be prevented or at least reduced in number by the use of a reduced-fat and therefore reduced-glycerol diet. Other families exhibit the benign form of isolated glycerol kinase deficiency. The affected individuals within these families have the biochemical features of this disorder but are asymptomatic. © 1996 Wiley-Liss, Inc.
Adaptive Mobile Cloud Computing to Enable Rich Mobile Multimedia Applications (2013)

With worldwide shipments of smartphones (487.7 million) exceeding PCs (414.6 million including tablets) in 2011, and in the US alone, more users predicted to access the Internet from mobile devices than from PCs by 2015, clearly there is a desire to be able to use mobile devices and networks like we use PCs and wireline networks today. However, in spite of advances in the capabilities of mobile devices, a gap will continue to exist, and may even widen, with the requirements of rich multimedia applications. Mobile cloud computing can help bridge this gap, providing mobile applications the capabilities of cloud servers and storage together with the benefits of mobile devices and mobile connectivity, possibly enabling a new generation of truly ubiquitous multimedia applications on mobile devices: Cloud Mobile Media (CMM) applications.
Induction of neurite outgrowth by v-src mimics critical aspects of nerve growth factor-induced differentiation. (1991)

PC12 cells treated with nerve growth factor (NGF) or infected with Rous sarcoma virus differentiate into sympathetic, neuronlike cells. To compare the differentiation programs induced by NGF and v-src, we have established a PC12 cell line expressing a temperature-sensitive v-src protein. The v-src-expressing PC12 cell line was shown to elaborate neuritic processes in a temperature-inducible manner, indicating that the differentiation process was dependent on the activity of the v-src protein. Further characterization of this cell line, in comparison with NGF-treated PC12 cells, indicated that the events associated with neurite outgrowth induced by these two agents shared features but could be distinguished by others. Both NGF- and v-src-induced neurite outgrowths were reversible. In addition, NGF and v-src could prime PC12 cells for NGF-induced neurite outgrowth, and representative early and late NGF-responsive genes were also induced by v-src. However, unlike NGF-induced neurite growth, v-src-induced neurite outgrowth was not blocked at high cell density. A comparison of phosphotyrosine containing-protein profiles showed that v-src and NGF each increase tyrosine phosphorylation of multiple cellular proteins. There was overlap in substrates; however, both NGF-specific and v-src-specific tyrosine phosphorylations were observed. One protein which was found to be phosphorylated in both the NGF- and v-src-induced PC12 cells was phospholipase C-gamma 1. Taken together, these results suggest that v-src's ability to function as an inducing agent may be a consequence of its ability to mimic critical aspects of the NGF differentiation program and raise the possibility that Src-like tyrosine kinases are involved in mediating some of the events triggered by NGF.