gebhart/patrepeval huggingface dataset:
Preparation of Conjugates of Oligodeoxynucleotides and Lipid Structures and Their Interaction with Low-Density Lipoprotein (1998)

The high expression level of receptors for low-density lipoprotein (LDL) on tumor cells makes LDL an attractive carrier for selective delivery of drugs to these cells. The aim of this study is to allow incorporation of oncogene-directed antisense oligodeoxynucleotides (ODNs) into the lipid moiety of LDL. Therefore, ODNs were conjugated with oleic acid, cholesterol, and several other steroid lipids. These latter steroid lipids were synthesized starting from bile acids and were varied in lipophilicity by attaching oleic acid ester structures. The lipid structures, activated as pentafluorophenyl esters, were conjugated in solution phase to 3'-amino-tailed ODNs. The ODNs conjugated with lithocholic acid, oleic acid, and cholesterol could easily be purified by reversed phase (RP)-HPLC. However, the ODNs conjugated with the oleoyl steroid ester structures irreversibly bound to the column material. These highly lipidic ODNs were separated from the nonconjugated ODN by electrophoresis in a 1% low-melting agarose gel containing 0.1% Tween 20. This method was found to be very effective in isolating the ODNs conjugated to the oleoyl steroid ester structures. The ODNs conjugated with cholesterol and the oleoyl esters of lithocholic and cholenic acid associated readily and nearly completely with LDL. However, the less lipidic ODNs and the ODN conjugated with the dioleoyl ester of chenodeoxycholic acid did not and did incompletely associate, respectively. Lithocholic acid and oleic acid are probably not sufficiently lipophilic to induce association with LDL, whereas the dioleoyl ester structure is probably too bulky and extended to allow partitioning into the lipid moiety of LDL. We conclude that several of the lipid-ODNs can associate readily with LDL, enabling delivery of oncogene-directed antisense ODNs via the LDL receptor pathway.
Efficient computation on oblivious RAMs (1990)

A machine is oblivious if the sequence in which it accesses memory locations is equivalent for any two programs with the same running time. For example, an oblivious Turing Machine is one for which the movement of the heads on the tapes is identical for each computation. (Thus, it is independent of the actual input.) What is the slowdown in the running time of any machine, if it is required to be oblivious?
Targeting of the Activation-Induced Cytosine Deaminase Is Strongly Influenced by the Sequence and Structure of the Targeted DNA (2005)

Activation-induced deaminase (AID) initiates immunoglobulin somatic hypermutation (SHM). Since in vitro AID was shown to deaminate cytosines on single-stranded DNA or the nontranscribed strand, it remained a puzzle how in vivo AID targets both DNA strands equally. Here we investigate the roles of transcription and DNA sequence in cytosine deamination. Strikingly different results are found with different substrates. Depending on the target sequence, the transcribed DNA strand is targeted as well as or better than the nontranscribed strand. The preferential targeting is not related to the frequency of AID hot spots. Comparison of cytosine deamination by AID and bisulfite shows different targeting patterns suggesting that AID may locally unwind the DNA. We conclude that somatic hypermutation on both DNA strands is the natural outcome of AID action on a transcribed gene; furthermore, the DNA sequence or structure and topology play major roles in targeting AID in vitro and in vivo. On the other hand, the lack of mutations in the first approximately 100 nucleotides and beyond about 1 to 2 kb from the promoter of immunoglobulin genes during SHM must be due to special conditions of transcription and chromatin in vivo.
Molecular chaperones involved in protein degradation in the endoplasmic reticulum: quantitative interaction of the heat shock cognate protein BiP with partially folded immunoglobulin light chains that are degraded in the endoplasmic reticulum. (1995)

In the absence of immunoglobulin heavy-chain expression, some immunoglobulin light (L) chains are retained and degraded within the cell. We investigated the fate of two different nonsecreted murine L chains which exhibit different half-lives (50 min and 3-4 hr). Our results demonstrate that both nonsecreted L chains are quantitatively bound to BiP as partially oxidized molecules. The kinetics of L-chain degradation coincided with those of L-chain dissociation from BiP, which suggests that these two processes are functionally related. L-chain degradation does not depend on vesicular transport, indicating that these soluble proteins are degraded in the endoplasmic reticulum (ER). In contrast, secreted L chains, which interact only transiently with BiP, are completely oxidized and are not degraded even when they are artificially retained in the ER. Our data support the model that, by means of BiP interaction, the ER degradation mechanism has the potential to discriminate between partially and completely folded molecules.
Neomycin biosynthesis: The incorporation of D-6-deoxy-glucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring. Postulated involvement of 2-deoxyinosose synthase in the biosynthesis. (1992)

D-[6-3H3]6-Deoxy-5-ketoglucose (10) and D-[5,6-3H2]6-deoxyglucose (11) were incorporated into neomycins B and C using a growing culture of Streptomyces fradiae. D-[6-3H]6-Deoxy-5-ketoglucose was incorporated into neomycin, as efficiently as the well established precursor D-glucose, and was found to label exclusively the 2-deoxystreptamine ring of the antibiotic. The results strengthened the previous proposals that in the formation of 2-deoxystreptamine the C-6 hydroxyl group of D-glucose is removed prior to the cyclisation reaction. Studies using the incorporation of D-[3-3H]glucose, D-[3,4-3H2]glucose and D-[5-3H]glucose into neomycin followed by the degradation of the latter established that in the biosynthesis of the 2-deoxystreptamine ring the C-4 and C-5 hydrogen atoms of glucose are removed. The loss of the C-4 hydrogen atom of the glucose is attributed to the formation of a 4-keto derivative which facilitates the removal of the C-5 hydrogen atom thus setting the stage for the expulsion of the C-6 hydroxyl group. The 5,6-olefinic intermediate formed in the process then undergoes cyclisation eventually releasing 2-deoxyinosose. The enzyme systems which participate in the conversion of D-glucose equivalent into 2-deoxyinosose may be described as 2-deoxyinosose synthase that in broad mechanistic terms resembles dehydroquinate synthase.
Nuclear Morphometry as a Predictor of Response to Therapy in Wilms Tumor: A Preliminary Report (1990)

Present therapy in Wilms tumor is based upon prognosis. Current trends suggest less intensive chemotherapy and/or radiation therapy for children with favorable histological disease who are considered at low risk for recurrence and increasing the amount of therapy for those with unfavorable histological tumors who are at high risk for recurrence. Currently, pathological stage and histological appearance are used to predict prognosis. We tested a new approach. Histological sections of surgical specimens were obtained from 9 children treated for unilateral Wilms tumor. All patients had favorable histological disease, and received postoperative chemotherapy and/or radiotherapy. These specimens were evaluated by nuclear morphometry with the Hopkins Morphometry System to determine if nuclear shape descriptors could distinguish children who responded to therapy from those whose tumor recurred. Nuclear roundness, ellipticity, convexity and bending energy accurately separated the groups. Nuclear morphometry may provide useful information that will aid in predicting which children with Wilms tumor will respond to therapy and warrants further investigations.
Cytokine networks in the skin. (1995)

Whereas some cytokines, such as interleukin-1 or tumor necrosis factor-alpha, have pleiotropic biologic properties, others seem to be more restricted in their biologic behavior. Interleukin-1 and tumor necrosis factor-alpha are known to induce the tissue accumulation of a mixed leukocyte infiltrate when injected into skin. Although both cytokines alone are not chemotactic, they can induce the production of secondary leukotactic cytokines in cells and therefore represent primary cytokines. A recently detected family of secondary and chemotactic cytokines, termed chemokines, now comprises 17 human members with leukocyte-selective chemotactic properties. Members of the so-called "C-X-C" chemokine subfamily, such as interleukin-8, Gro-alpha, and possibly the gamma-interferon-inducible protein IP-10, seem to be important for neutrophil- and/or T-lymphocyte-selective accumulation in inflamed skin because of their more neutrophil-or T-lymphocyte-, but not monocyte- or eosinophil-chemotactic properties. On the other hand, members of the "C-C" chemokine subfamily, such as monocyte chemotactic protein-1, RANTES, macrophage inflammatory protein-1 alpha, and MARC/monocyte chemotactic protein-3, attract monocytes, T-lymphocyte forms and subsets, eosinophils, and basophils, but not neutrophils. The cell-specific chemotactic properties as well as the release pattern, which seems to be at least in part tissue cell- and stimulus-specific, point to a possible role in chronic skin diseases, explaining parts of the disease-characteristic tissue infiltrates. The recent detection of novel chemokines with T-lymphocyte-type and sub-population-specific chemotactic properties may facilitate understanding of disease-characteristic patterns of T-lymphocyte accumulation, including homing phenomena.
Emerging technology: electrical stimulation in obstructive sleep apnoea. (2015)

Electrical stimulation (ES) of the upper airway (UAW) dilator muscles for patients with obstructive sleep apnoea (OSA) has been used for several decades, but in recent years research in this field has experienced a renaissance; the results of several studies have triggered a steady rise in the interest in this topic. Prospective trials, although still lacking a sham-controlled and randomised approach, have revealed the potential of ES. Hypoglossal nerve stimulation (HNS) leads to a significant reduction in the apnoea-hypopnoea index and the oxygen desaturation index (ODI). There are similar results published from feasibility studies for transcutaneous ES. A limitation of HNS remains the invasive procedure, the costs involved and severe adverse events, while for the non-invasive approach complications are rare and limited. The limiting step for transcutaneous ES is to deliver a sufficient current without causing arousal from sleep. Despite the progress up to date, numerous variables including optimal stimulation settings, different devices and procedures remain to be further defined for the invasive and the non-invasive method. Further studies are required to identify which patients respond to this treatment. ES of the UAW dilator muscles in OSA has the potential to develop into a clinical alternative to continuous positive airway pressure (CPAP) therapy. It could benefit selected patients who fail standard therapy due to poor long-term compliance. It is likely that international societies will need to review and update their existing guidance on the use of ES in OSA.
Human Milk Oligosaccharides Attenuate Antigen–Antibody Complex Induced Chemokine Release from Human Intestinal Epithelial Cell Lines (2018)

This study provides evidence for direct effects of HMOs in addition to their prebiotic role and demonstrates, for the first time, modulation of Ag-IgE complex activation of human epithelial cells that may have important implications for food-allergy. The study also reinforces the concept that structurally different oligosaccharides have distinct biological activities. In determining the composition of infant formula, addition of oligosaccharides with specific structures may provide direct modulation of immune responses and potentially attenuate symptoms or development of food allergy.
Anti-glycophorin single-chain Fv fusion to low-affinity mutant erythropoietin improves red blood cell-lineage specificity (2010)

The presence of erythropoietin (Epo) receptors on cells besides red blood cell precursors, such as cancer cells or megakaryocyte precursors, can lead to side effects during Epo therapy including enhanced tumor growth and platelet production. It would be ideal if the action of Epo could be limited to erythroid precursors. To address this issue, we constructed single-chain variable fragment (scFv)-Epo fusion proteins that used the anti-glycophorin 10F7 scFv amino-terminal to Epo analogues that would have minimal activity alone. We introduced the Epo mutations N147A, R150A and R150E, which progressively weakened receptor affinity in the context of Epo alone, as defined by cell proliferation assays using TF-1 or UT-7 cells. Fusion of these mutant proteins to the 10F7 scFv significantly rescued the activity of the mutant proteins, but had a relatively small effect on wild-type Epo. For example, fusion to the 10F7 scFv enhanced the activity of Epo(R150A) by 10- to 27-fold, while a corresponding fusion to wild-type Epo enhanced its activity only up to 2.7-fold. When glycophorin was blocked by antibody competition or reduced by siRNA-mediated inhibition of expression, the activity of 10F7 scFv-Epo(R150A) was correspondingly reduced, while such inhibition had essentially no effect on the activity of 10F7 scFv-Epo(wild-type). In addition, potent stimulation of Epo receptors by 10F7 scFv-Epo(R150A) was observed in long-term proliferation and viability assays. Taken together, these results indicate that a combination of targeting and affinity modulation can be used to engineer forms of Epo with enhanced cell-type specificity.
Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. (1992)

Two forms of cyclooxygenase are known to be present in eukaryotic organisms: a cyclooxygenase (COX-1) first purified from ram seminal vesicles encoded by a 2.8-kilobase mRNA, and a newly discovered mitogen-inducible cyclooxygenase (COX-2) encoded by a 4-kilobase mRNA. Expression of these two forms of the enzyme in rat alveolar macrophages stimulated with lipopolysaccharide was investigated by 1) determining the activity of newly synthesized enzyme after inactivating the endogenous enzyme with aspirin; 2) comparing levels of newly synthesized enzyme proteins in cells treated with or without lipopolysaccharide; and 3) assessing the expression of the mRNAs encoding COX-1 and COX-2. Levels of enzyme proteins were assessed by Western blot analysis and immunoprecipitation of 35S-labeled enzyme using two different antibodies, one specific for COX-2 and the other recognizing both forms of the enzyme but preferentially recognizing COX-1. We report here that the enhanced cyclooxygenase activity induced by the bacterial lipopolysaccharide in rat alveolar macrophages is caused by selective expression of the COX-2. Expression of COX-2 in macrophages stimulated by lipopolysaccharide was completely inhibited by dexamethasone, whereas COX-1 was unaffected. In resting unstimulated macrophages, only COX-1 but not COX-2 was detected. Levels of mRNA for the COX-2 in macrophages were increased, but those of the COX-1 were not affected by lipopolysaccharide as assessed by reverse transcription coupled with polymerase chain reaction. These results indicate that increased synthesis of prostaglandins and thromboxanes in lipopolysaccharide-stimulated macrophages results from selective expression of COX-2.
Breast cancer survival and chemotherapy: A support vector machine analysis (2000)

A linear support vector machine (SVM) is used to extract 6 features from a total of 31 features in a dataset of 253 breast cancer patients. Five features are nuclear features obtained during a non-invasive diagnostic procedure while one feature, tumor size, is obtained during surgery. The linear SVM selected the 6 features in the process of classifying the patients into node-positive (patients with some metastasized lymph nodes) and nodenegative (patients with no metastasized lymph nodes). Node-positive patients are typically those who undergo chemotherapy. The 6 features were then used in a Gaussian kernel nonlinear SVM to classify the patients into three prognostic groups: good (node-negative), intermediate (1 to 4 metastasized nodes) and poor (more than 4 metastasized nodes). Very well separated Kaplan-Meier survival curves were constructed for the three groups with pairwise p-value of less than 0.009 based on the logrank statistic. Patients in the good prognostic group had the highest survival, while patients in the poor prognostic group had the lowest. The majority (72.8%) of the good group did not receive chemotherapy, while the majority (87.5%) of the poor group received chemotherapy. Just over half (56.7%) of the intermediate group received chemotherapy. New patients can be assigned to one of these three prognostic groups with its associated survival curve, based only on 6 features obtained before and during surgery, but without the potentially risky procedure of removing lymph nodes to determine how many of them have metastasized.
The class II MHC-restricted presentation of endogenously synthesized ovalbumin displays clonal variation, requires endosomal/lysosomal processing, and is up-regulated by heat shock (1992)

LB27.4 cells (a B lymphoblastoid APC) were transfected with a plasmid containing an OVA cDNA. Functional analysis of six independent clones yielded three patterns of MHC-restricted presentation of the endogenously synthesized OVA. A clone displayed either: 1) strong class I and class II-restricted presentation, 2) strong class I but little or no class II-restricted presentation or, 3) only a modest class I-restricted presentation. There was no clonal variation in class II-restricted presentation of exogenous Ag or in the amount of surface class I or II molecules. Heat shock increased the presentation of endogenous but not exogenous Ag with class II. These results indicate that an endogenously synthesized Ag both constitutively and during heat shock can gain access to the class II, MHC-restricted, presentation pathway. The amount of OVA synthesized by a cell correlated with whether OVA-class II complexes were detected. However, the amount of OVA secreted into the extracellular fluid was not sufficient to sensitize APC, which suggests that endogenously synthesized OVA enters the class II pathway of Ag presentation by an intracellular route rather than by an extracellular/reuptake route. Also, the functional and quantitative analysis of the clones suggests that endogenously synthesized OVA was presented more efficiently with class I as compared to class II-MHC molecules. Leupeptin and chloroquine inhibited the class II-restricted presentation of endogenously synthesized OVA. Together these results indicate that endogenously synthesized OVA can gain access to an endosomal/lysosomal compartment via an intracellular route and be processed and presented in association with class II-MHC molecules.
Red wine contains a potent inhibitor of phenolsulphotransferase. (1985)

Many ethanolic drinks, especially red wine, contain potent inhibitors of phenolsulphotransferase. At a dilution of 1/75 from the original beverage, extracts from six types of red wine inhibited human platelet phenolsulphotransferase P by a mean of 99% and human platelet phenolsulphotransferase M by 12%. Such extracts had no significant effect on rat liver monoamine oxidase A or human platelet monoamine oxidase B. The inhibitors, which have not yet been identified, can be extracted into ethyl acetate at acid or neutral pH. Thus, they are not monoamines. Flavonoid phenols are plausible candidates. As phenolsulphotransferase M and P are involved in the metabolism of many phenols, including drugs, the inhibition of these enzymes could result in the enhancement of pharmacological potency and have important clinical consequences.
Introduction to Web services architecture (2002)

This paper introduces the major components of, and standards associated with, the Web services architecture. The different roles associated with the Web services architecture and the programming stack for Web services are described. The architectural elements of Web services are then related to a real-world business scenario in order to illustrate how the Web services approach helps solve real business problems.
Stimulation of granulopoiesis in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor: assessment of two routes of administration. (1990)

We administered Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor to 61 patients with malignancy, 36 of whom had normal peripheral blood counts and 25 of whom had peripheral cytopenia due to underlying bone marrow disease, to compare the efficacy of two different routes of administration to stimulate the in vivo granulopoiesis: i.e., continuous i.v. infusion and s.c. injection. Three well-tolerated dose levels were investigated. Application of granulocyte-macrophage colony-stimulating factor resulted in dose-dependent increases in circulating neutrophils, eosinophils, and monocytes and an increase in bone marrow cellularity, irrespective of route of administration. In some patients, mild side effects, including bone pain, dyspnea, flu-like symptoms, and a decrease of platelet counts, were recorded, but they were less pronounced when the hormone was administered subcutaneously.
MORC4, a novel member of the MORC family, is highly expressed in a subset of diffuse large B‐cell lymphomas (2007)

The OX-TES-4 antigen originally elicited an antibody response in 50% of diffuse large B-cell lymphoma (DLBCL) patients but not in control subjects. OX-TES-4 is encoded by a novel gene, MORC4, located at chromosome Xq22.3. The MORC4 protein contains a HATPase-c domain, CW zinc finger motif, nuclear localisation signals and a nuclear matrix-binding domain, together with a coiled-coil region. MORC4 mRNA is widely expressed at low levels in normal tissues, showing highest expression levels in placenta and testis. mRNA levels were increased in non-germinal centre-derived DLBCL and Hodgkin lymphoma cell lines, compared with germinal centre-derived DLBCL cell lines and normal B cells. Nineteen DLBCL patients (66%) expressed significantly higher levels of MORC4 mRNA than normal B cells (P = 0.0031). The differential expression of MORC4 identifies this molecule as a potential lymphoma biomarker, whose overexpression may contribute to the immunological recognition of MORC4 by a subgroup of DLBCL patients.
The Nature of the Binding Site for Prothrombinase at the Platelet Surface as Revealed by Lipolytic Enzymes (1982)

The nature of the receptor for the prothrombinase complex at the surface of non-activated platelets was investigated by measuring the platelet prothrombin-converting activity wih a chromogenic substrate assay, after treatment of the platelets with various phospholipases or three different proteolytic enzymes. Platelet prothrombin-converting activity only decreased after treatment with those phospholipases which are able to hydrolyse phospholipids in the intact platelet and also have the ability to degrade negatively charged phospholipids, phosphatidylserine and phosphatidylinositol. Those phospholipases which do hydrolyse phospholipids in the intact platelet but have no activity towards phosphatidylserine (and phosphatidylinositol) produce an increase in the platelet prothrombin-converting activity. Proteolytic treatment of platelets with trypsin, chymotrypsin or papain did not result in a decrease of prothrombin-converting activity. It is concluded that negatively charged phosphatidylserine and possibly phosphatidylinositol are involved in the prothrombin-converting activity of non-activated platelets. We could not demonstrate the involvement of platelet membrane proteins in a receptor for the components of the prothrombinase complex.