gebhart/patrepeval huggingface dataset:
Engineering neonatal Fc receptor-mediated recycling and transcytosis in recombinant proteins by short terminal peptide extensions (2012)

The importance of therapeutic recombinant proteins in medicine has led to a variety of tactics to increase their circulation time or to enable routes of administration other than injection. One clinically successful tactic to improve both protein circulation and delivery is to fuse the Fc domain of IgG to therapeutic proteins so that the resulting fusion proteins interact with the human neonatal Fc receptor (FcRn). As an alternative to grafting the high molecular weight Fc domain to therapeutic proteins, we have modified their N and/or C termini with a short peptide sequence that interacts with FcRn. Our strategy was motivated by results [Mezo AR, et al. (2008) Proc Natl Acad Sci USA 105:2337-2342] that identified peptides that compete with human IgG for FcRn. The small size and simple structure of the FcRn-binding peptide (FcBP) allows for expression of FcBP fusion proteins in Escherichia coli and results in their pH-dependent binding to FcRn with an affinity comparable to that of IgG. The FcBP fusion proteins are internalized, recycled, and transcytosed across cell monolayers that express FcRn. This strategy has the potential to improve protein transport across epithelial barriers, which could lead to noninvasive administration and also enable longer half-lives of therapeutic proteins.
Serum sex hormone binding globulin and testosterone binding after estradiol administration, castration, and their combination in men with prostatic carcinoma. (1979)

We measured serum sex hormone binding globulin (SHBG) binding capacity, the index of testosterone binding to SHRG, and the serum concentrations of testosterone, 5 alpha-dihydrotestosterone, and estradiol in 16 patients treated for advanced prostatic carcinoma in order to evaluate the effectiveness of various therapeutic regimes in reducing total and biologically active androgen in blood. Polyestradiol phosphate (Estradurin, 80 mg im as a monthly injection) treatment alone is not as efficient as castration in reducing serum testosterone and 5 alpha-dihydrotestosterone. There was no clear difference between the castration and combination treatment (castration followed by polyestradiol phosphate administration) groups in this respect. It is apparent that Estradurin treatment alone and in combination with castration results in small but significant increases in SHBG binding capacity, whereas this parameter did not alter after castration alone. All three forms of treatment resulted in relatively similar significant increases in the index of testosterone binding to SHBG. The rather mild effect of Estradurin on the parameters measured may be attributable to the binding of the exogenous estradiol to SHBG, which thus greatly reduces its biologic activity. We concluded that castration is clearly more effective in reducing the amount of biologically active testosterone than Estradurin and the combination of these treatments has little influence on further reducing total or biologically active circulating testosterone.
“Então, eu fui à luta!”: repensando as representações e práticas econômicas de grupos populares a partir de uma trajetória de ascensão social (2009)

This text raises questions that emerged while developing research on the process, currently underway in Brazil, in which popular groups’ attain increased access to financial services and mechanisms and the credit supply available to low income people has expanded. Using one informant’s trajectory as our guiding thread, we will take a critical look at some of the original premises of our research and attempt to put together new research hypotheses. The latter are meant to relativize differences and take a more nuanced approach to the borders which we had initially supposed could be drawn around the logics that guide the economic and financial life of individuals of popular classes and the principles that reign actions of the agents who provide them with financial services. Keywords: Economic Anthropology, Economic Sociology, credit and consumption, popular classes and economic practices, social mobility.
A Hippocampal Cognitive Prosthesis: Multi-Input, Multi-Output Nonlinear Modeling and VLSI Implementation (2012)

This paper describes the development of a cognitive prosthesis designed to restore the ability to form new long-term memories typically lost after damage to the hippocampus. The animal model used is delayed nonmatch-to-sample (DNMS) behavior in the rat, and the "core" of the prosthesis is a biomimetic multi-input/multi-output (MIMO) nonlinear model that provides the capability for predicting spatio-temporal spike train output of hippocampus (CA1) based on spatio-temporal spike train inputs recorded presynaptically to CA1 (e.g., CA3). We demonstrate the capability of the MIMO model for highly accurate predictions of CA1 coded memories that can be made on a single-trial basis and in real-time. When hippocampal CA1 function is blocked and long-term memory formation is lost, successful DNMS behavior also is abolished. However, when MIMO model predictions are used to reinstate CA1 memory-related activity by driving spatio-temporal electrical stimulation of hippocampal output to mimic the patterns of activity observed in control conditions, successful DNMS behavior is restored. We also outline the design in very-large-scale integration for a hardware implementation of a 16-input, 16-output MIMO model, along with spike sorting, amplification, and other functions necessary for a total system, when coupled together with electrode arrays to record extracellularly from populations of hippocampal neurons, that can serve as a cognitive prosthesis in behaving animals.
Tetracycline-Inducible Packaging Cell Line for Production of Flavivirus Replicon Particles (2003)

We have previously developed replicon vectors derived from the Australian flavivirus Kunjin that have a unique noncytopathic nature and have been shown to direct prolonged high-level expression of encoded heterologous genes in vitro and in vivo and to induce strong and long-lasting immune responses to encoded immunogens in mice. To facilitate further applications of these vectors in the form of virus-like particles (VLPs), we have now generated a stable BHK packaging cell line, tetKUNCprME, carrying a Kunjin structural gene cassette under the control of a tetracycline-inducible promoter. Withdrawal of tetracycline from the medium resulted in production of Kunjin structural proteins that were capable of packaging transfected and self-amplified Kunjin replicon RNA into the secreted VLPs at titers of up to 1.6 x 10(9) VLPs per ml. Furthermore, secreted KUN replicon VLPs from tetKUNCprME cells could be harvested continuously for as long as 10 days after RNA transfection, producing a total yield of more than 10(10) VLPs per 10(6) transfected cells. Passaging of VLPs on Vero cells or intracerebral injection into 2- to 4-day-old suckling mice illustrated the complete absence of any infectious Kunjin virus. tetKUNCprME cells were also capable of packaging replicon RNA from closely and distantly related flaviviruses, West Nile virus and dengue virus type 2, respectively. The utility of high-titer KUN replicon VLPs was demonstrated by showing increasing CD8(+)-T-cell responses to encoded foreign protein with increasing doses of KUN VLPs. A single dose of 2.5 x 10(7) VLPs carrying the human respiratory syncytial virus M2 gene induced 1,400 CD8 T cells per 10(6) splenocytes in an ex vivo gamma interferon enzyme-linked immunospot assay. The packaging cell line thus represents a significant advance in the development of the noncytopathic Kunjin virus replicon-based gene expression system and may be widely applicable to the basic studies of flavivirus RNA packaging and virus assembly as well as to the development of gene expression systems based on replicons from different flaviviruses.
Nanoscale Size Effect of Magnetic Nanocrystals and Their Utilization for Cancer Diagnosis via Magnetic Resonance Imaging (2005)

Since the use of magnetic nanocrystals as probes for biomedical system is attractive, it is important to develop optimal synthetic protocols for high-quality magnetic nanocrystals and to have the systematic understanding of their nanoscale properties. Here we present the development of a synthetically controlled magnetic nanocrystal model system that correlates the nanoscale tunabilities in terms of size, magnetism, and induced nuclear spin relaxation processes. This system further led to the development of high-performance nanocrystal-antibody probe systems for the diagnosis of breast cancer cells via magnetic resonance imaging.
Targeting sphingosine-1-phosphate for cancer therapy (2006)

This review summarises some important new findings that implicate sphingosine-1-phosphate (S1P) as a potent tumorigenic and angiogenic agent released from cancerous tumours into the tumour microenvironment. Also explored is the novel concept that bioactive lipid signalling molecules, like S1P, can themselves be targets for rational drug design, thereby opening up an entire class of lipidomic-based therapeutics for oncology and other human diseases.
BILJNI SVIJET KROZ BROJKE (2014)

Z nate li to su mnogostanini autotrofni fotosintetski organizmi, odnosno orga- nizmi graeni od velikog broja stanica koji samostalno stvaraju hranu, i to koritenjem Suneve svjetlosti?Dakako,
Brain-inspired computing exploiting carbon nanotube FETs and resistive RAM: Hyperdimensional computing case study (2018)

We demonstrate an end-to-end brain-inspired hyperdimensional (HD) computing nanosystem, effective for cognitive tasks such as language recognition, using heterogeneous integration of multiple emerging nanotechnologies. It uses monolithic 3D integration of carbon nanotube field-effect transistors (CNFETs, an emerging logic technology with significant energy-delay product (EDP) benefit vs. silicon CMOS [1]) and Resistive RAM (RRAM, an emerging memory that promises dense non-volatile and analog storage [2]). Due to their low fabrication temperature (<;250°C), CNFETs and RRAM naturally enable monolithic 3D integration with fine-grained and dense vertical connections (exceeding various chip stacking and packaging approaches) between computation and storage layers using back-end-of-line inter-layer vias [3]. We exploit RRAM and CNFETs to create area-and energy-efficient circuits for HD computing: approximate accumulation circuits using gradual RRAM reset operation (in addition to RRAM single-bit storage) and random projection circuits that embrace inherent variations in RRAM and CNFETs. Our results demonstrate: 1. pairwise classification of 21 European languages with measured accuracy of up to 98% on >20,000 sentences (6.4 million characters) per language pair. 2. One-shot learning (i.e., learning from few examples) using one text sample (~100,000 characters) per language. 3. Resilient operation (98% accuracy) despite 78% hardware errors (circuit outputs stuck at 0 or 1). Our HD nanosystem consists of 1,952 CNFETs integrated with 224 RRAM cells.
The Claisen Acylation of Methyl Ketones with Branched Chain Aliphatic Esters1 (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Claisen Acylation of Methyl Ketones with Branched Chain Aliphatic Esters1Eugene H. Man, Frederic W. Swamer, and Charles R. HauserCite this: J. Am. Chem. Soc. 1951, 73, 3, 901–903Publication Date (Print):March 1, 1951Publication History Published online1 May 2002Published inissue 1 March 1951https://doi.org/10.1021/ja01147a005RIGHTS & PERMISSIONSArticle Views661Altmetric-Citations24LEARN 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 InReddit PDF (411 KB) Get e-Alerts Get e-Alerts
Evidence for a Two-Step Mechanism Involved in the Formation of Covalent HC·TSG-6 Complexes (2006)

IalphaI and TSG-6 interact to form a covalent bond between the C-terminal Asp alpha-carbon of an IalphaI heavy chain (HC) and an unknown component of TSG-6. This event disrupts the protein-glycosaminoglycan-protein (PGP) cross-link and dissociates IalphaI. In simple terms the interaction involves 5 components: (i) the IalphaI HCs, (ii) bikunin, (iii) chondroitin sulfate chain, (iv) TSG-6, and (v) divalent cations. To understand the molecular mechanism of complex formation, the effect of these were separately examined. The data show that although the mature covalent cross-link between the HCs and TSG-6 only involves the C-terminal Asp residue, the native fold of both IalphaI and TSG-6 was essential for the reaction to occur. Similarly, complex formation was prevented if the chondroitin sulfate chain was cleaved, releasing bikunin but maintaining the HC1 and HC2 PGP cross-links. In contrast, releasing the majority of the bikunin protein moiety by limited proteolysis did not prevent complex formation. An analysis of the divalent-cation requirements revealed two distinct interactions between IalphaI and TSG-6: (i) a noncovalent manganese, magnesium, or calcium-independent interaction between TSG-6 and the chondroitin sulfate chain (Kd 180 nM) and (ii) a covalent manganese, magnesium, or calcium-dependent interaction generating HC1 x TSG-6, HC2 x TSG-6, and high molecular weight (HMW) IalphaI. Significantly, both free TSG-6 and HC x TSG-6 complexes were able to bind the chondroitin sulfate chain suggesting that the sites on TSG-6 were distinct. On the basis of these findings, we propose a two-step reaction mechanism involving two putative binding sites. Initially, a cation-independent interaction between TSG-6 and the chondroitin sulfate chain is formed at site 1. Subsequently, a cation-dependent transesterification occurs, generating the covalent HC x TSG-6 cross-link at another site, site 2.
The Epidemiology of Alcohol, Marijuana, and Cocaine Use Among Mexican American, Puerto Rican, Cuban American, and Other Latin American Eighth-Grade Students in the United States: 1991–2002 (2005)

A better understanding of the homogeneity and heterogeneity of drug use patterns within and between Hispanic groups should assist in the development of prevention programs.
Salivary statherin. Dependence on sequence, charge, hydrogen bonding potency, and helical conformation for adsorption to hydroxyapatite and inhibition of mineralization. (1992)

The structural domains of salivary statherin that are partly responsible for the protection and recalcification of tooth enamel were examined with respect to charge, sequence, hydrophobicity, hydrogen bonding potential, and conformation. Several fragments of statherin, 1-15 (SN15), 5-15 (SN11), 15-29 (SM15), 29-43 (SC15), 19-43 (SC25), and analogs of the N-terminal 15-residue sequence, where phosphoserines at positions 2 and 3 have been replaced by Ser (SNS15) and Asp (SNA15), respectively, were synthesized. The abilities of these fragments to adsorb at hydroxyapatite (HAP) surfaces and to inhibit its mineralization in supersaturated solutions were determined and compared with those of the whole statherin molecule, reported previously. The conformational preferences of the fragments both in aqueous and nonaqueous solutions were examined by circular dichroism. The highly charged N-terminal SN15 fragment has the greatest adsorption to HAP as compared with statherin and all other fragments. Its mineralization inhibitory activity is significantly greater than those of other fragments and comparable with that of the whole molecule. The dephosphorylated N-terminal fragment SNS15 shows a decreased tendency to adhere to and inhibit the formation of HAP, as compared with SN15. However, the substitution of Asp residues in place of phosphoserines (SNA15), restores the binding affinity and crystal growth inhibition properties, suggesting that the negative charge density at the N-terminal rather than any specific interaction of the phosphate group is important for HAP surface interactions. The C-terminal SC15 and SC25 fragments elicit a much higher affinity for HAP surface than that of the middle sequence (SM15), indicating that hydrogen bonding potential of the C-terminal sequence also contributes to the interaction of statherin with HAP. CD studies provide evidence that the N-terminal SN15 fragment has a strong tendency to adopt an ordered helical conformation, whereas the shorter N-terminal sequence, middle, and C-terminal fragments are structurally flexible and prefer to adopt scattered turn structures or unordered random conformations in organic and aqueous solutions. Collectively, the data indicate that the negative charge density, sequence (1-15), and helical conformation at the N-terminal region of statherin are important for its surface interaction with HAP.
On the atomic hydrogen line shapes in a plane-cathode obstructed glow discharge (1994)

In order to investigate the charge-transfer reaction between Ar+ and H2 which is important for the shape of hydrogen Balmer lines and to clarify the pathway of this reaction, the study of charge-transfer reaction Ar+ + Cu in argon-copper, argon-copper-hydrogen and neon-copper-hydrogen plasma of a plane-cathode hollow anode glow discharge was undertaken. It is shown that Ar+(2P1/2) + H2 reaction is the main source of H2+ ions in our plasma.
Inference Policies (1990)

It is suggested that an AI inference system should reflect an inference policy that is tailored to the domain of problems to which it is applied -- and furthermore that an inference policy need not conform to any general theory of rational inference or induction. We note, for instance, that Bayesian reasoning about the probabilistic characteristics of an inference domain may result in the specification of an nonBayesian procedure for reasoning within the inference domain. In this paper, the idea of an inference policy is explored in some detail. To support this exploration, the characteristics of some standard and nonstandard inference policies are examined.
Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers (2000)

Carbonic anhydrase XII (CA XII) is a transmembrane glycoprotein with an active extracellular CA domain that is overexpressed on cell surfaces of certain cancers. Its expression has been linked to tumor invasiveness. To characterize its catalytic properties, we purified recombinant secretory forms of wild-type and mutant CA XIIs. The catalytic properties of these enzymes in the hydration of CO(2) were measured at steady state by stopped-flow spectrophotometry and at chemical equilibrium by the exchange of (18)O between CO(2) and water determined by mass spectrometry. The catalysis of CO(2) hydration by soluble CA XII has a maximal value of k(cat)/K(m) at 34 microM(-1) small middle dots(-1), which is similar to those of the membrane-associated CA IV and to soluble CA I. The pH profiles of this catalysis and the catalyzed hydrolysis of 4-nitrophenylacetate indicate that the pK(a) of the zinc-bound water in CA XII is 7.1. His64 in CA XII acts as a proton shuttle residue, as evidenced by the reduced rate constant for proton transfer in the mutants containing the replacements His64 --> Ala and His64 --> Arg, as well as by the selective inhibition of the proton transfer step by cupric ions in wild-type CA XII. The catalytic rate of CO(2) hydration by the soluble form of CA XII is identical with that of the membrane-bound enzyme. These observations suggest a role for CA XII in CO(2)/HCO(3)(-) homeostasis in cells in which it is normally expressed. They are also compatible with a role for CA XII in acidifying the microenvironment of cancer cells in which CA XII is overexpressed, providing a mechanism for CA XII to augment tumor invasiveness and suggesting CA XII as a potential target for chemotherapeutic agents.
Combination approach of SMOTE and biased-SVM for imbalanced datasets (2008)

A new approach to construct the classifiers from imbalanced datasets is proposed by combining SMOTE (synthetic minority over-sampling technique) and Biased-SVM (biased support vector machine) approaches. A dataset is imbalanced if the classification categories are not approximately equally represented. Often real-world data sets are predominately composed of ldquonormalrdquo examples with only a small percentage of ldquoabnormalrdquo or ldquointerestingrdquo examples. The cost of misclassifying an abnormal (interesting) example into a normal example is often much higher than that of the reverse error. It was known as a means of increasing the sensitivity of a classifier to the minority class using SMOTE over-sampling in minority class. But in this paper, it gives a good means of increasing the sensitivity of a classifier to the minority class by using SMOTE approaches within support vectors. As for support vector over-sampling, this paper proposes two different over-sampling algorithms to deal with the support vectors being over-sampled by its neighbors from the k nearest neighbors, not only within the support vectors but also within the entire minority class. Some experimental results confirms that the proposed combination approach of SMOTE and biased-SVM can achieve better classifier performance.
Infusion of anti-B7.1 (CD80) and anti-B7.2 (CD86) monoclonal antibodies inhibits murine graft-versus-host disease lethality in part via direct effects on CD4+ and CD8+ T cells (1996)

Efficient T cell proliferation requires costimulation via CD28/B7 or other pathways. Graft-vs-host disease (GVHD) is caused by activated donor T cells. We have found that the infusion of anti-B7.1 (CD80) + anti-B7.2 (CD86) mAb is effective in eliminating GVHD lethality induced by either CD8+ or CD4+ T cells. Donor CD4+ and CD8+ T cell expansion was inhibited by almost 100-fold as measured by enumerating thoracic duct lymphocytes (TDL) obtained early post-transplant. TDL retained anti-host responsiveness indicating that not all T cells were anergic. Although anti-CD80 or anti-CD86 mAb individually were ineffective in preventing CD8+ T cell GVHD lethality, each mAb was partially effective in CD4+ T cell-mediated GVHD. Because CD80 expression was found to be up-regulated on donor CD4+ TDL post-transplant, the GVHD capacity of donor CD4+ T cells deficient in CD80 was tested and found to be reduced similarly to that seen with anti-CD80 mAb. These studies demonstrate that anti-CD80 + anti-CD86 mAb infusion is effective in preventing GVHD lethality by inhibiting donor CD4+ or CD8+ T cell expansion and provide the first evidence that CD80 expression on donor T cells is critical for optimal GVHD lethality.