gebhart/patrepeval huggingface dataset:
The Biological Basis of and Strategies for Clinical Xenotransplantation (1994)

Recent discoveries have suggested that the exchange of multiple leukocyte lineages between grafts and host and subsequent long-term chimerism in both is the seminal mechanism of the acceptance of organs transplanted from the same (allografts) or different species (xenografts). This insight suggests new strategies which may allow xenotransplantation, the principal obstacle to which has been humoral rejection. We have defined humoral rejection as a family of complement activation syndromes afflicting allografts and xenografts in which there is a strong (but not invariable) association with performed antigraft antibodies, invariable evidence of complement activation, histopathologic stigmas of vascular endothelial damage, and a concomitant local or systemic coagulopathy. The generic descriptive term hyperacute rejection is a misnomer because a slow-motion version of the same "humoral" process can occur with some allografts and is the rule with the so-called concordant species xenotransplantations. The pathway of experience and discovery leading to this conclusion shows clearly that the distinction frequently made between allograft versus xenograft humoral rejection does not actually exist in principle, but only in details and intensity. Breaking down this barrier to xenotransplantation, whether or not it is associated with antibodies, is unrealistic. However, the possibility of avoiding the barrier has been exposed by showing that animal organs can be humanized, with a mixed donor and recipient cell population similar to the chimerism seen in long surviving allografts or even with complete leukocyte replacement. Pilot experiments in rodents suggest that organs from fully xenogeneic chimeras can be made into xenogeneic targets that are no more provocative of complement activation than allografts when they are transplanted into the donor bone marrow species. Although the validity of this concept of organ xenograft preparation is only at the pilot stage of verification, there is reason to suspect that the complement trigger of humoral rejection can be thereby disarmed. If this can be accomplished, independent evidence suggests that cellular rejection can be controlled with conventional T-cell directed immunosuppression, perhaps even with surprising ease. The potential subtle liability of synthetic products of xenogeneic parenchymal cells is not yet known.
Analysis of the Plasma Peptidome from Pancreas Cancer Patients Connects a Peptide in Plasma to Overexpression of the Parent Protein in Tumors (2009)

Blood circulates through nearly every organ including tumors. Therefore, plasma is a logical source to search for tumor-derived proteins and peptides. The challenge with plasma is that it is a complex bodily fluid composed of high concentrations of normal host proteins that obscure identification of tumor-derived molecules. To simplify plasma, we examined a low molecular weight (LMW) fraction (plasma peptidome) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. In the plasma peptidome of patients with ductal adenocarcinoma of the pancreas (DAP), a prominent peptide was identified from the QSOX1 parent protein. This peptide is stable in whole blood over 24 h and was present in 16 of 23 DAP patients and 4 of 5 patients with intraductal papillary mucinous neoplasm (IPMN). QSOX1 peptides were never identified in the plasma peptidome from 42 normal healthy donors using the same methods. Immunohistochemical staining of DAP tissue sections with anti-QSOX1 antibody shows overexpression of QSOX1 in tumor but not in adjacent stroma or normal ducts. Three of four pancreas tumor cell lines also express QSOX1 protein by Western blot analysis. This is the first report of QSOX1 peptides in plasma from DAP patients and makes the rare connection between a peptide in plasma from cancer patients and overexpression of the parent protein in tumors.
Localization of cytochrome c-binding domain on NADPH-cytochrome P-450 reductase. (1986)

A covalent complex between purified rat liver microsomal NADPH-cytochrome P-450 reductase and horse cytochrome c was formed through cross-linking studies with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide at low ionic strength. The purified cross-linked derivative shows that this product is a 1:1 complex containing one molecule each of the flavoprotein and cytochrome. The covalent complex had almost completely blocked the electron transfer from NADPH to exogenous cytochrome c or the rabbit liver microsomal cytochrome P-450 induced by phenobarbital, indicating that the cross-linked cytochrome c covers the electron-accepting site of the reductase. These results suggest that the covalently cross-linked derivative is a valid model of the noncovalent electron transfer complex. Although the exact number and site of the cross-linked location were not determinable, in cytochrome c the amide bond originates from Lys-13 and in reductase it might be at any one of six different side chain carboxyl groups in the two neighboring cluster acidic residues, Asp-207, -208, and -209, and Glu-213, Glu-214, and Asp-215. It is therefore proposed that the six clustered carboxyl groups on reductase are in an exposed location near the area where one heme edge comes close to the molecular surface.
Searching for Human Longevity Genes: The Future History of Gerontology in the Post-genomic Era (2001)

Over the last 30 years, a number of genetic and environmental factors that lead to decreased length of life have been identified. Unfortunately, much less progress has been achieved in identifying genes associated with longevity that protect from common diseases or slow the aging process. Recent compelling evidence supports a role for important genetic and environmental interactions on longevity in lower organisms. Although less is known in humans, commonality in molecular and biological processes, evolutionary arguments, and epidemiological data would strongly suggest that similar mechanisms also apply. The completion of the Human Genome Project and the rapid innovations in technology will make possible the identification of human longevity-assurance genes. This article reviews such evidence, its implications for the identification of human longevity-assurance genes, and the significance of finding longevity genes to human health and disease.
Optimal Design Methodlogy for LLC Resonant Converter (2006)

Although LLC resonant converter can achieve wide operation range with high efficiency, lack of design methodology makes it difficult to be implemented. In this paper, based on the theoretical analysis on the operation principles during normal condition and holdup time, the relationship between converter efficiency and operation range with different circuit parameters has be revealed. An optimal design methodology has been developed based on the revealed relationship. A 1MHz, 1kW LLC converter is designed to verify the proposed method.
Radiofrequency penetration and absorption in the human body: Limitations to high‐field whole‐body nuclear magnetic resonance imaging (1987)

This study presents experimental results about the effective depth of penetration and about the radiofrequency (rf) power absorption in humans as a function of frequency. The frequency range investigated covers 10 up to 220 MHz. For the main part, the results were derived from bench measurements of the quality factor Q, and of the resonance frequency shift due to the loading of the coil. Different types of head-, body-, and surface coils were investigated loaded with volunteers or metallic phantoms. For spin-echo imaging at 2 T (85 MHz), the local specific absorption rate (SAR) was found to be approximately equal to 0.05 W/kg using a pi pulse of 1-ms duration and pulse repetition time TR = 1 s. Measurements of the quality factor Q as a function of frequency show that the SAR depends upon the frequency f according to approximately f2.15. The effective depth of rf penetration as derived drops from 17 cm at 85 MHz to 7 cm at 220 MHz. Head imaging with B1 penetrating from practically all sides into the object should be possible up to 220 MHz (5 T) with SAR values staying within the local limit of 2 W/kg as set by the FDA. Whole-body imaging of large subjects as well as surface coil imaging is depth limited above 100-MHz frequency. Perturbation methods are applied in order to separate the total rf power deposition in the patient into dielectric and magnetic contributions. The observed effects due to interactions of rf magnetic fields with biological tissue contradict predictions based on homogeneous tissue models. A refined tissue model with regions of high electrical conductivity, subdivided by quasi-insulating adipose layers, provides a rationale for a better understanding of the underlying processes. At frequencies below 100 MHz, the rf power deposition in patients is apparently more evenly distributed over the exposed body volume than currently assumed.
Eigengene networks for studying the relationships between co-expression modules (2007)

Eigengene networks can be effective and biologically meaningful tools for studying the relationships between modules of a gene co-expression network. The proposed methods may reveal a higher order organization of the transcriptome. R software tutorials, the data, and supplementary material can be found at the following webpage: http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/EigengeneNetwork.
Developments in the treatment of chronic hepatitis C (2002)

Hepatitis C virus is the most common chronic, blood-bourne infection, affecting 170 million people worldwide, approximately 3% of the global population. Of those infected with hepatitis C virus, 50 - 85% will develop chronic hepatitis C. Although hepatitis C is primarily a disease of the liver, a diagnosis is currently defined by the presence of the hepatitis C virus and treatment success is defined by the clearance of the virus. IFN-alpha is currently the mainstay of chronic hepatitis C therapy; the antiviral and anti-inflammatory components of IFN target both the infectious and the hepatic manifestations of the disease. However, even in combination with ribavirin, interferon therapy is not fully efficacious. Recently, the search for a more effective treatment has led investigators to optimise interferon therapy by developing pegylated interferons. Challenges facing our current treatment of hepatitis C virus include lack of efficacy in patients with difficult-to-treat disease, such as patients with cirrhosis or infected with hepatitis C virus genotype 1 (who represent a majority of US hepatitis C virus infections), the toxicity of combination therapy, the expense and difficulty of therapy and the poor reception of these treatments by many patients. The development of new hepatitis C antiviral agents is critical to our management of this disease. A number of approaches are under investigation, including long-acting interferons, immunomodulators, antifibrotics, specific hepatitis C virus-derived enzyme inhibitors, drugs that either block hepatitis C virus antigen production from RNA or prevent normal processing of hepatitis C virus proteins and other molecular approaches to treating hepatitis C virus, such as ribozymes and antisense oligonucleotides.
Correlated Label Propagation with Application to Multi-label Learning (2006)

Many computer vision applications, such as scene analysis and medical image interpretation, are ill-suited for traditional classification where each image can only be associated with a single class. This has stimulated recent work in multi-label learning where a given image can be tagged with multiple class labels. A serious problem with existing approaches is that they are unable to exploit correlations between class labels. This paper presents a novel framework for multi-label learning termed Correlated Label Propagation (CLP) that explicitly models interactions between labels in an efficient manner. As in standard label propagation, labels attached to training data points are propagated to test data points; however, unlike standard algorithms that treat each label independently, CLP simultaneously co-propagates multiple labels. Existing work eschews such an approach since naive algorithms for label co-propagation are intractable. We present an algorithm based on properties of submodular functions that efficiently finds an optimal solution. Our experiments demonstrate that CLP leads to significant gains in precision/recall against standard techniques on two real-world computer vision tasks involving several hundred labels.
Efficient p53 Activation and Apoptosis by Simultaneous Disruption of Binding to MDM2 and MDMX (2007)

The p53 tumor suppressor plays a key role in protection against malignant transformation. MDM2 and MDMX are important regulators of the transcriptional activity and stability of p53 by binding to its NH(2) terminus. Recent studies suggest that inhibition of both MDM2 and MDMX is necessary for robust activation of p53 in certain tumor cells. However, small-molecule MDM2 inhibitors such as Nutlin fail to inhibit MDMX despite significant homology between the two proteins. The therapeutic efficacy of such compounds may be compromised by MDMX overexpression. To evaluate the feasibility and biological effects of simultaneously disrupting p53 binding to MDM2 and MDMX, we used phage display to identify a novel peptide that can inhibit p53 interactions with MDM2 (IC(50) = 10 nmol/L) and MDMX (IC(50) = 100 nmol/L). Expression of a scaffold protein (thioredoxin) displaying this peptide sequence by adenovirus disrupts both MDM2 and MDMX interaction with p53, resulting in efficient p53 activation, cell cycle arrest, and apoptosis of tumor cells overexpressing MDM2 and MDMX. Intratumoral injection of the adenovirus also induces growth suppression of tumor xenografts in mice in a p53-dependent fashion. These results show the therapeutic potential of targeting both MDM2 and MDMX in cancer, and provide a novel structural motif for the design of potent p53 activators.
Irreversible coupling of immunoglobulin fragments to preformed vesicles. An improved method for liposome targeting. (1982)

Rabbit Fab' antibody fragments were covalently couple to preformed large unilamellar vesicles using a new sulfhydryl-reactive phospholipid derivative N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine (MPB-PE). A highly efficient reaction between the sulfhydryl group on each Fab' fragment and the maleimide moiety of MPB-PE molecules incorporated at a low concentration in vesicle bilayers led to the formation of a highly stable Fab'-vesicle linkage. Coupling ratios in excess of 250 micrograms of Fab'/mumol of vesicle phospholipid were reproduciably obtained without vesicle aggregation. Bound Fab' fragments did not elute from vesicles in serum or in the presence of reducing agents (dithiothreitol or mercaptoethanol). Vesicles bearing Fab' fragments raised against specific human erythrocyte surface determinants bound selectively to human erythrocytes under physiological conditions (isotonic medium containing 50% human serum, pH 7.4) with minimal leakage of vesicle contents. Advantages of the present coupling method are discussed in relationship to our effects to optimize the properties of liposomes as a carrier system.
Isolation of p53‐target genes and their functional analysis (2004)

Mutations of the p53 gene are the most common genetic alterations found in human cancers, and are known to play crucial roles in tumor development and progression. The p53 gene encodes a protein functioning as a transcription factor, and the biological functions of p53 are manifested through the activities of its downstream genes. Identification of these downstream genes involved in the p53-signaling pathway should provide more detailed insight into the molecular mechanisms that mediate tumor-suppressor activities, as well as various responses to cellular stress. We have been attempting to isolate p53-target genes by means of various approaches, including differential display, cDNA microarray analysis, and direct cloning of the p53-binding sequences from human genomic DNA. Here I review our recent work on isolation of p53-target genes and their functional analysis. The physiological functions of p53-target genes include apoptosis (GML, p53AIP1, and STAG1), DNA repair (p53R2), inhibition of angiogenesis (BAI1), re-entry into the cell cycle (p53RFP), oxidative stress (CSR), and determination of cell fate (p53RDL1).
Using a knowledge cache for interactive discovery of association rules (1999)

Association rule mining is a valuable decision support technique that can be used to analyze customer preferences, buying patterns, and product correlations. Current systems are however handicapped by the long processing times required by mining algorithms that make them unsuitable for interactive use. In this paper, we propose the use of a knowledge cache that can reduce the response time by several orders of magnitude. Most of the performance gain comes from the idea of guaranteed support that allows us to completely eliminate database accesses in a large number of cases. Using this cache, the time taken to answer a query is proportional to just the size of the result, rather than to the size of the database. Cache replacement is best done by a benefit-metric based strategy that can easily adapt to changing query patterns.
A dysfunctional movement protein of tobacco mosaic virus that partially modifies the plasmodesmata and limits virus spread in transgenic plants (1993)

A chimeric gene encoding a dysfunctional tobacco mosaic virus (TMV) movement protein (MP) mutant lacking amino acids 3, 4 and 5 (MPΔ3–5), was expressed in transgenic Nicotiana tabacum Xanthi and Xanthi NN plants. Immunogold labeling studies of tissues from transgenic plants indicated that while wild‐type MP accumulated in the plasmodesmata, MPΔ3–5 did not. Tissue fractionation studies confirmed that only a low level of the mutant MP accumulated in the cell wall‐enriched fraction compared with the accumulation of the wild‐type MP. Dye coupling studies showed that MPΔ3–5 enabled the movement between leaf mesophyll cells of a fluorescently labeled dextran of 3 kDa, while 9.4 kDa molecules failed to move. In contrast, in transgenic plants expressing the wild‐type MP gene the 9.4 kDa probe did move from cell to cell. Seedlings from self‐fertilized transgenic plants were inoculated with TMV and observed for disease symptoms. Transgenic Xanthi NN plants that expressed the MPΔ3–5 gene developed fewer and smaller necrotic local lesions compared with control plants following inoculation with TMV. Transgenic Xanthi nn plants were delayed in the development of systemic symptoms. Inoculating the transgenic plants with TMV‐RNA, and the tobamo‐viruses TMGMV and SHMV, essentially produced the same results, i.e. inhibition of disease development. These results demonstrate that transgenic plants expressing an inactive MP can inhibit virus disease spread presumably by interfering with its cell‐to‐cell movement.
Neonatal Signs as Predictors of Cerebral Palsy (1979)

Signs of neonatal neurologic dysfunction, recorded in approximately 40,000 infants, were evaluated prospectively for their ability to predict later motor handicap. Tenfold to 33-fold increases in risk of cerebral palsy (CP) were observed in surviving children with any one of the following characteristics: birth weight less than 2,000 gm, head circumference more than 3 SD above or below the mean, five minute Apgar score of 3 or less, diminished activity or diminished cry lasting for more than one day, thermal instability, need for gavage feeding, hypotonia or hypertonia, single or multiple apneic episodes, or hematocrit less than 40%. Of worse portent, with relative risks exceeding 50, were neonatal seizures or Apgar scores of 3 or less at ten minutes or later. These characteristics were also markers of considerable risk of early death. For 0.5% of surviving infants, an overall impression of abnormality of brain function during the nursery period was recorded by the attending physician; there was a 99-fold increase in CP among these children.
Scherrer after sixty years: A survey and some new results in the determination of crystallite size (1978)

Existing knowledge about Scherrer constants is reviewed and a summary is given of the interpretation of the broadening arising from small crystallites. Early work involving the half-width as a measure of breadth has been completed and Scherrer constants of simple regular shapes have been determined for all low-angle reflections (h2 + k2 + l2 ≤ 100) for four measures of breadth. The systematic variation of Scherrer constant with hkl is discussed and a convenient representation in the form of contour maps is applied to simple shapes. The relation between the `apparent' crystallite size, as determined by X-ray methods, and the `true' size is considered for crystallites having the same shape. If they are of the same size, then the normal Scherrer constant applies, but if there is a distribution of sizes, a modified Scherrer constant must be used.
The T Cell Cytolytic Molecules FasL and TRAIL are Required for Thymic GVHD (141.14) (2009)

Abstract Thymic graft-versus-host-disease (tGVHD) is an important contributor to impaired T cell reconstitution in patients with GVHD. We analyzed molecules relevant for T cell trafficking and cytolytic function in tGVHD. Thymic output and cellularity were inversely proportional to numbers of mature donor T cells in the allograft, suggesting that tGVHD severity was inversely associated with thymic function. Upon adoptive transfer of CFSE-labeled donor T cells, we noted that thymus-infiltrating alloreactive donor T cells were largely fast-proliferating and highly activated. These T cells infiltrated the thymus within one week after allogeneic bone marrow transplantation. We analyzed T cells in tGVHD with mice deficient for certain molecules, and found that the trafficking molecules CCR9, β7 integrin, and PSGL-1 were all partially required for tGVHD, while L-selectin and αE integrin subunit may be dispensable. Similarly, we examined the role of T cell cytolytic pathways for tGVHD, and found that FasL and tumor necrosis factor associated apoptosis inducing ligand (TRAIL) were required for tGVHD, but that perforin and TNF were dispensable. As host thymic stroma may be an important target for donor alloreactive T cells, we assessed the expression of the death receptors Fas and DR5 in thymic stroma from normal and irradiated mice, and found that endothelium and fibroblasts, as well as epithelial cells upregulated the expression of both Fas and DR5 after irradiation. FLIP, which is a negative regulator of Fas ligand and TRAIL mediated apoptosis, was also downregulated after irradiation. Our study suggests that TRAIL, which has previously been shown to be important in graft-versus-tumor activity, may also be important for mediating GVHD.
<title>Design methodology for programmable video signal processors</title> (1997)

This paper presents a design methodology for a high- performance, programmable video signal processor (VSP). The proposed design methodology explores both technology-driven hardware tradeoffs and application-driven architectural tradeoffs for optimizing cost and performance within a class of processor architectures. In particular, this methodology allows concurrent consideration of these competing factors at different levels of design sophistication, ranging from early design exploration towards full processor simulation. We present the results of this methodology for an aggressive very-long-instruction-word (VLIW) video signal processor design and discuss its utility for other programmable signal processor designs.