gebhart/patrepeval huggingface dataset:
Complement Factor H–ligand interactions: Self-association, multivalency and dissociation constants (2011)

Factor H (FH) is the major plasma regulator of the central complement protein C3b in the alternative pathway of complement activation. The elucidation of the FH interactions with five major ligands (below) is complicated by their weak μM dissociation constants K(D) and FH multivalency. We present the first survey of all the K(D) values for the major FH-ligand interactions and critically review their physiological significance. (i) FH self-association is presently well-established. We review multiple data sets that show that 5-14% of FH is self-associated in physiological conditions. FH self-association is significant for both laboratory investigations and physiological function.(ii) The FH-C3b complex shows low M affinity, meaning that the complex is not fully formed in plasma. In addition, C3, its hydrolysed form C3u, and its cleaved forms C3b and C3d show multimerisation. Current data favour a model when two C3b molecules bind independently to one FH molecule, as opposed to a1:1 stoichiometry where FH wraps itself around C3b.(iii) Heparin is often used as an analogue of the polyanionic host cell surface. The FH-heparin complex also shows a low M affinity, again meaning that complexes are not fully formed in vivo. The oligomeric FH-heparin complexes clarify a two-site interaction model of FH with host-cell surfaces.(iv) Reinvestigation of the FH and C-reactive protein (CRP) interaction revealed that this can only occur in plasma when CRP levels are elevated during acute-phase conditions. Given that CRP binds more weakly to the His402 allotype of FH than the Tyr402 allotype, this suggested a link with age-related macular degeneration (AMD).(v) FH activity is inhibited by zinc, which causes FH to aggregate strongly. High levels of bioavailable zinc occur in sub-retinal pigment epithelial deposits which lead to AMD. Excess zinc binds weakly to a central region of FH, explaining how zinc inhibits FH regulation of C3b.
Immunological markers of anti-tumor dendritic cells vaccine efficiency in patients with non-small cell lung cancer. (2013)

Immunological markers established in our investigation can be used for estimation of DC-immunotherapy efficiency. The results of our research are very promising, but these data should be confirmed in further studies with a large cohort of patients.
Retinoids and ovarian cancer (2000)

Each year, an estimated 26,000 women in the United States are diagnosed with ovarian cancer. During any given year, approximately 14,500 women die from this disease. Ovarian cancer is the seventh most common cancer in women worldwide, after breast, cervix, colon/rectum, stomach, corpus uteri, and lung cancers. In the U.S., ovarian cancer is the second most common gynecologic cancer, and is the fourth leading cause of solid tumor cancer deaths among women. Currently, postoperative chemotherapy of ovarian cancer is still suboptimal. Drug resistance is a common problem resulting in only 20 approximately 30% overall 5-year survival rates. Clearly, continued development of alternative therapeutic strategies is essential for the management of this fatal disease. A number of recent studies have suggested that retinoids may play a potential role as an ovarian cancer chemotherapeutic agent. Retinoids, the natural and synthetic derivatives of vitamin A, have been shown to inhibit the growth of human ovarian cancer cells both in vivo and in culture. This review will initially summarize what is known about the pathological and molecular characteristics of ovarian carcinoma. It will then describe retinoid metabolism and the role of the cellular and nuclear retinoid binding proteins in mediating retinoid action. Following this general review of retinoids and their function, data supporting the role of retinoic acid as a suppresser of ovarian carcinoma cell growth will be presented. Particular attention will be paid to studies suggesting that members of the RB family of proteins and RB2/p130, in particular, are the molecular targets responsible for retinoid mediated inhibition of ovarian carcinoma cell growth. This review will then conclude with a brief discussion of two synthetic retinoids, 4 HPR R(fenretinide) and AHPN/CD437, which have been shown to induce apoptosis in ovarian tumor cells. It will be clear from the studies summarized in this review that retinoids represent a potentially powerful alternative to present chemotherapeutic approaches to the treatment of late stage ovarian cancer.
Large Scale T cell receptor repertoire sequencing of murine CD8+ T cells. (144.5) (2010)

Abstract Theoretically, mice can produce 1015 possible αβ T cell receptors (TCRs), with over 106 TCR clonotypes present at a given time. Data driven estimates based on a rigorous analysis of this massive complex repertoire have not been done due to the cost of obtaining a large set of TCR sequences. The advent of next generation DNA sequencing platforms (Illumina, SOLiD, 454) has brought TCR sequence analysis into the realm of possibility. Matching the platform with the TCR template’s unique characteristics is essential. Each T cell rearranges its genome to generate a unique TCR (VDJ recombination), with nongermline bases enzymatically produced at the junctions. Attempts to “assemble” TCR sequences from short reads (35bp, Illumina) that do not span the recombination junctions have introduced an assembly conundrum. However, the 454 pyrosequencing platform’s 250bp sequence reads generate full TCR clonotypes with no need for overlap assembly. Herein, we provide the first large scale C57Bl/6 mouse TCR β repertoire on a long read platform (Roche 454). To illustrate our methods strength, we have generated hundreds of thousands of TCRs from multiple B6 mice. To estimate the procedures error rates we have sequenced TCRs from a recombinase deficient TCR transgenic mouse (P14). This technique enables organism level analysis of T cell lineage specification, selection, and regulation during development and in disease states (infectious, autoimmune, graft and vaccine responses).
Side-chain hydrophobicity scale derived from transmembrane protein folding into lipid bilayers (2011)

The transfer free energies of the twenty natural amino acid side chains from water to phospholipid bilayers make a major contribution to the assembly and function of membrane proteins. Measurements of those transfer free energies will facilitate the identification of membrane protein sequences and aid in the understanding of how proteins interact with membranes during key biological events. We report the first water-to-bilayer transfer free energy scale (i.e., a "hydrophobicity scale") for the twenty natural amino acid side chains measured in the context of a native transmembrane protein and a phospholipid bilayer. Our measurements reveal parity for apolar side-chain contributions between soluble and membrane proteins and further demonstrate that an arginine side-chain placed near the middle of a lipid bilayer is accommodated with much less energetic cost than predicted by molecular dynamics simulations.
Sustained Release of Nerve Growth Factor from Biodegradable Polymer Microspheres (1992)

Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.
A new network-based intelligent surveillance system (2002)

Aiming at the shortcomings of prevalent visual surveillance systems, an intelligent surveillance system which can accomplish automatic detection and classification of moving objects by making use of the personal computer and network system is presented. This kind of surveillance system is provided with high performance/price ratio and the ability to realize all kinds of complex algorithms. In addition, the mature PC network makes it convenient to centrally manage the alarm log and image database so as to reduce the cost of every detection computer. Especially, the leader or administrator can view the interesting alarm log or image at his own office by a LAN (local area network) and intranet connection. Because of complex scenes and lots of disturbance in outdoor environments, such concepts as detecting block, extraction function, feature data and some key techniques such as projection histogram of silhouette pattern, accumulation based on space-time information and geometric model based on edge detection are presented to solve the difficulty of human body recognizing and decrease the ratio of missing alarm and false alarm.
Mixed-Salt Effects on the Ionic Conductivity of Lithium-Doped PEO-Containing Block Copolymers (2011)

We demonstrate a simple, yet effective, mixed-salt method to increase the room temperature ionic conductivity of lithium-doped block copolymer electrolyte membranes by suppressing the crystalline phases in the conducting block. We examined a mixed-salt system of LiClO4 and LiN(SO2CF3)2 (LiTFSI) doped into a lamellae-forming poly(styrene-b-ethylene oxide) (PS–PEO) diblock copolymer. The domain spacings, morphologies, thermal behavior, and crystalline phases of salt-doped PS–PEO samples were characterized, and the ionic conductivities of block copolymer electrolytes were obtained through ac impedance measurements. Comparing the ionic conductivity profiles of salt-doped PS–PEO samples at different mixed-salt ratios and total salt concentrations, we found that the ionic conductivity at room temperature can be improved by more than an order of magnitude when coinhibition of crystallite growth is promoted by the concerted behavior of the PEO:LiClO4 and PEO:LiTFSI phases. Additionally, we examined the influence of mixed-salt ratio and total salt concentration on copolymer energetics, and we found that the slope of the effective interaction parameter (χeff) vs salt concentration in our lamellae-forming PS–PEO system was lower than that reported for a cylinder-forming PS–PEO system due to the balance between chain stretching and salt segregation in the PEO domains.
Phorbol diester receptor copurifies with protein kinase C. (1983)

The phorbol diester receptor present in the particulate fraction of rat brain was solubilized by divalent ion chelation in the absence of detergents. The soluble receptor was partially purified by (NH4)2SO4 precipitation, DEAE-cellulose, and gel filtration chromatography. The purified receptor required exogenous phospholipid for activity and displayed a Kd of 7 nM for [3H]phorbol 12, 13-dibutyrate. Biologically active phorbol analogs inhibited binding, whereas inactive analogs did not. The Ca2+-dependent, phospholipid-sensitive protein kinase C copurified with the phorbol receptor. Purified protein kinase C was activated directly by phorbol 12-myristate 13-acetate in the presence of phospholipid.
A Low Power Tunable Delay Element Suitable for Asynchronous Delays of Burst Information (2008)

A low-energy delay element based on a thyristor-like circuit is proposed that is suitable for concatenation in dense arrays in order to delay narrowly spaced burst timing information with accompanying data bits. Handshaking is built into the cell to ensure no information is lost. There is no static power dissipation aside from leakage and the energy consumption is not a function of the achieved delay. A design fabricated in a UMC 90 nm CMOS process has delays from 5 ns to 1 mus, as tuned through an analog input port, require an energy consumption of 50 fJ/delay event with a supply voltage of 1 V.
www.dermanities.com (2004)

Dermanities, an open-access electronic humanities journal for dermatologists, is a peaceful place on the Web. Designed to entertain, challenge, and heal, it is a slim but carefully wrought literary magazine of the type felicitously found in the corners of bookstores for serious readers.
Trusteeship and Canada's Indians (1976)

Trusteeship and Canada's Indians It has been suggested recently by some of those concerned with putting forward claims on behalf of Canada's Indians that Canada stands in the position of a trustee, and the contention has been made that this relationship is not merely one of municipal concern, but that the international trusteeship system extends to them. In so far as the North American Indians are concerned, the idea of trusteeship may be traced back to the comment of Chief Justice Marshall in Cherokee Nation v. Georgia:1 [The Indians] are in a state of pupilage; their relation to the United States resembles that of a ward to his guardian. They look to the government for protection; rely upon its kindness and its power... Other United States Supreme Court judgments were to the same effect. Ex parte Crow Dog2 concerned the interpretation of the Treaty of 1868 with the Sioux, and its interconnection with Chapter IV of Title XXVIII of the Revised Statutes entitled 'Government for Indian Country.' Speaking for the Court, Justice Matthews stated They were to be subjected to the laws of the United States not in the sense of citizens but, as they had always been, as wards subject to guardians; ... as a dependent community who were in a state of pupilage... The purpose of this 'wardship' may be seen in the comments of Justice Miller in U.S. v. Kagama3: The Indian tribes are the wards of the nation ... Because of local ill-feeling, the people of the states where they are found are often their deadliest enemies. From their very weaknesses and helplessness .... there arises the duty of protection and with it the power. Clearly, therefore, the Supreme Court looked upon the tribes, not the individuals who normally form the subject of guardian/ward relationships, as being in a special capacity. The judges did not say that the common law concept of this relationship governed the situation, for in the words of Marshall it merely 'resembled' it. Moreover, the rights of a ward as against his guardian were, in the normal way, protected through the medium of the courts. What later commentators tend to overlook when having recourse to the comments of the Chief Justice is that he went on to say: ... If it be true that the Cherokee Nation have rights, this is not the tribunal in which those rights are to be asserted. If it be true that wrongs have been inflicted, and that still greater are to be apprehended, this is not the tribunal which can redress the past or prevent the future.
Fatty acid synthesis is a therapeutic target in human liposarcoma (2010)

Liposarcomas (LS) are mesenchymal tumors that can recur after surgical resection and often do not respond to presently available medical therapies. This study demonstrates the dependence of LS on de novo long-chain fatty acid synthesis for growth. Lipogenesis can be impaired by inhibiting the activities of lipogenic enzymes, including acetyl CoA-carboxylase (ACC) and fatty acid synthase (FASN), or by suppressing the expression of key genes involved in the pathway and its regulation. The FASN inhibitors cerulenin and orlistat reduced the growth of two LS cell lines (LiSa2, SW872), as did inhibition of ACC with soraphen A. CDDO-Me, a synthetic triterpenoid, suppressed expression of Spot 14 and FASN genes and likewise inhibited LS cell growth. Importantly, the anti-proliferative effect of each agent was prevented by the co-administration of palmitate, the major product of cellular long-chain fatty acid synthesis. In stark contrast to LS cells, these compounds had no effect on the growth of fibroblasts. Four biochemically distinct agents that target critical points in the fatty acid synthetic pathway exert anti-proliferative effects on LS cells, and rescue of cell growth by palmitic acid suggests that reduced tumor cell lipogenesis mediates the growth inhibition. These findings warrant further studies aimed at the clinical exploitation of the dependence of LS cell growth on fatty acids.
When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function (1995)

As a way of delineating different levels of cancer pain severity, we explored the relationship between numerical ratings of pain severity and ratings of pain's interference with such functions as activity, mood, and sleep. Interference measures were used as critical variable to grade pain severity. We explored the possibility that pain severity could be classified into groupings roughly comparable to mild, moderate, and severe. Our hypothesis was that mild, moderate, and severe pain would differentially impair cancer patients' function. We were able to identify boundaries among these categories of pain severity in terms of their interference with function. We also examined the extent to which cancer patients from different language and cultural groups differ in their self-reported interference as a function of pain severity level. We found optimal cutpoints that form 3 distinct levels of pain severity that can be defined on a 0-10-point numerical scale. We determined that, based on the degree of interference with cancer patients' function, ratings of 1-4 correspond to mild pain, 5-6 to moderate pain, and 7-10 to severe pain. Our analysis illustrates that the pain severity-interference relationship is non-linear. These cutpoints were the same for each of the national samples in our analysis, although there were slight differences in the specific interference items affected by pain. These cutpoints might be useful in clinical evaluation, epidemiology, and clinical trials.
Humanized Mouse Model of Cooley's Anemia (2008)

A novel humanized mouse model of Cooley's Anemia (CA) was generated by targeted gene replacement in embryonic stem (ES) cells. Because the mouse does not have a true fetal hemoglobin, a delayed switching human gamma to beta(0) globin gene cassette (gammabeta(0)) was inserted directly into the murine beta globin locus replacing both adult mouse beta globin genes. The inserted human beta(0) globin allele has a mutation in the splice donor site that produces the same aberrant transcripts in mice as described in human cells. No functional human beta globin polypeptide chains are produced. Heterozygous gammabeta(0) mice suffer from microcytic anemia. Unlike previously described animal models of beta thalassemia major, homozygous gammabeta(0) mice switch from mouse embryonic globin chains to human fetal gamma globin during fetal life. When bred with human alpha globin knockin mice, homozygous CA mice survive solely upon human fetal hemoglobin at birth. This preclinical animal model of CA can be utilized to study the regulation of globin gene expression, synthesis, and switching; the reactivation of human fetal globin gene expression; and the testing of genetic and cell-based therapies for the correction of thalassemia.
DropBot: An open-source digital microfluidic control system with precise control of electrostatic driving force and instantaneous drop velocity measurement (2013)

We introduce DropBot: an open-source instrument for digital microfluidics (http://microfluidics.utoronto.ca/dropbot). DropBot features two key functionalities for digital microfluidics: (1) real-time monitoring of instantaneous drop velocity (which we propose is a proxy for resistive forces), and (2) application of constant electrostatic driving forces through compensation for amplifier-loading and device capacitance. We anticipate that this system will enhance insight into failure modes and lead to new strategies for improved device reliability, and will be useful for the growing number of users who are adopting digital microfluidics for automated, miniaturized laboratory operation.
Stability and functional effectiveness of phosphorothioate modified duplex DNA and synthetic ‘mini-genes’ (1995)

Several gene transfer techniques that employ 'naked DNA' molecules have recently been developed and numerous gene therapy protocols that make use of 'naked-DNA' have been proposed. We studied the possibility of enhancing the stability of 'naked DNA vectors' and thus also gene transfer and expression efficiencies, by constructing phosphorothioate (PS-) double strand DNA molecules and functional transcription units. We first synthesized short PS-double strand DNA molecules by the annealing of two complementary, 35 nt long, oligonucleotides. The accessibility of DNA modifying enzymes to this molecule was significantly decreased: T4-ligase and kinase activity were respectively reduced up to 1/2 and to 1/6, as compared to the normal phosphodiester molecule. Nucleolytic stability was increased either to purified enzymes (DNase I and Bal31) or to incubations in fresh serum, cell culture medium or in muscle protein extract. Phosphorothioate end-capped complete eukaryotic transcription units (obtained by Taq polymerase amplification with PS-primers) were not significantly protected from nucleolytic attack. On the contrary, synthetic transcription units, 'mini genes', obtained by Taq amplification with 1, 2 or 3 PS-dNTP substitutions, were resistant to DNase I and Bal31 nucleolytic activity. Transcription efficiency, driven by the T7 promoter, was 96.5, 95 and 33.5% (respectively with 1, 2 or 3 substitutions), as compared to the normal phosphodiester molecules.
Broadening mechanisms, gain, and low linewidth enhancement factor in InAs quantum-dot lasers (2000)

Summary form only given. A detailed understanding of many optical characteristics of quantum dot lasers remains in a nascent stage. However, its density of states function suggests many intriguing features. Here we present experimental investigations of homogeneous broadening, gain, and linewidth enhancement factor measurements in quantum dot laser diodes. A gain model that describes the evolution of the emission spectra along with subsidiary mode suppression is also presented.
Critical InfoVis (2013)

As information visualization is increasingly used to raise awareness about social issues, difficult questions arise about the power of visualization. So far the research community has not given sufficient thought to how values and assumptions pervade information visualization. Taking engaging visualizations as a starting point, we outline a critical approach that promotes disclosure, plurality, contingency, and empowerment. Based on this approach, we pose some challenges and opportunities for visualization researchers and practitioners.