gebhart/patrepeval huggingface dataset:
Somatic reversion/suppression in Duchenne muscular dystrophy (DMD): evidence supporting a frame-restoring mechanism in rare dystrophin-positive fibers. (1992)

Many Duchenne muscular dystrophy (DMD) patients are known to have rare staining dystrophin-positive fibers, termed "revertants." The precise etiology of these rare fibers is unknown. The most likely explanation, however, is somatic mosaicism or somatic reversion/suppression. Immunocytochemistry was performed on serial sections from deleted and nondeleted patients, with a panel of antibodies--9219, 1377, 9218, and Dys-2--that span dystrophin. Both familial and nonfamilial patients possessed revertants. Either the same clusters or individual revertant fibers stained with amino- and carboxyl-terminal antibodies in all 14 DMD patients. In patients with deletions, revertants did not stain with antibodies raised to polypeptide sequences within the deletion. These results indicate that positively staining fibers are not the result of somatic mosaicism in deleted patients. Five of 10 patients without deletions had revertant fibers. In two of these patients, the revertant fibers did not stain with antibody 9218, which was generated against amino acids 2305-2554 and which corresponds to exons 48-52. The remaining antibodies from the panel stained the same fibers on separate serial sections in these two patients. The most likely mechanism giving rise to these positively staining fibers is a second site in-frame deletion. Antibodies generated to polypeptide sequences within deletions can be used to control for the natural occurrence of revertant fibers in myoblast transfer studies and may be useful in the detection of point mutations.
Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats (1998)

We have recently shown that long-term, but not acute, treatment with lithium robustly protects cultured CNS neurons against excitotoxicity mediated by NMDA receptors. Since NMDA receptor over-excitation has been strongly implicated in the ischemic brain injury, we examined the effects of chronic lithium treatment on neurological deficit and brain infarct induced by occlusion of the left middle cerebral artery in rats. Subcutaneous injection of LiCl for 16 days significantly improved neurological deficits, including abnormal posture and hemiplegia, measured 24 h after artery occlusion. Importantly, the size of ischemic infarct was reduced by 56% after lithium pretreatment. These results raise the possibility that lithium may be useful for reducing focal ischemia-induced brain damage and neurological abnormalities.
DJ-MC: A Reinforcement-Learning Agent for Music Playlist Recommendation (2014)

In recent years, there has been growing focus on the study of automated recommender systems. Music recommendation systems serve as a prominent domain for such works, both from an academic and a commercial perspective. A fundamental aspect of music perception is that music is experienced in temporal context and in sequence. In this work we present DJ-MC, a novel reinforcement-learning framework for music recommendation that does not recommend songs individually but rather song sequences, or playlists, based on a model of preferences for both songs and song transitions. The model is learned online and is uniquely adapted for each listener. To reduce exploration time, DJ-MC exploits user feedback to initialize a model, which it subsequently updates by reinforcement. We evaluate our framework with human participants using both real song and playlist data. Our results indicate that DJ-MC's ability to recommend sequences of songs provides a significant improvement over more straightforward approaches, which do not take transitions into account.
Reduction in Cerebral Atrophy Associated with Ethyl-Eicosapentaenoic Acid Treatment in Patients with Huntington's Disease (2008)

Ultra-pure ethyl-eicosapentaenoic acid (ethyl-EPA), a semi-synthetic ethyl ester of eicosapentaenoic acid, is associated with clinical improvement in motor functioning in Huntington's disease. The aim was to determine the extent to which it might reduce the rate of progress of cerebral atrophy. High-resolution cerebral magnetic resonance imaging scans were acquired at baseline, 6 months and 1 year in up to 34 patients with stage I or II Huntington's disease who took part in a randomized, double-blind, placebo-controlled trial of ethyl-EPA. For each subject and each pair of structural images, the two-timepoint brain volume change was calculated in a double-blind manner. Significant group-level reductions in brain atrophy were observed in the head of the caudate nucleus and the posterior thalamus. These findings show that treatment with ethyl-EPA is associated with significant reduction in brain atrophy, particularly in the caudate and thalamus. No other drug tested in Huntington's disease has shown this effect.
Assessment of in vivo effectiveness of tumoricidal chemotherapy and radiation therapy by serial analysis of tumor-associated urinary antigen titers in patients with sarcoma. (1982)

Serial measurements of tumor-associated antigens in the urine of patients with sarcoma who received preoperative intra-arterial doxorubicin and radiation therapy were assayed by microcomplement fixation. Changes in urinary antigen titer as a result of therapy were compared to pretreatment samples and were correlated with clinicopathologic evidence of in situ tumor cell destruction. Of the 53 patients with sarcoma studied, 44 had clinicopathologic evidence of tumor destruction induced by the preoperative therapy, and all 44 had a fourfold or greater rise in the level of urinary antigens during the treatment period. The other nine patients had no evidence of tumor destruction and antigen titers remained unchanged. Results suggested that tumoricidal therapy released tumor-associated antigens which could be detected in urine by microcomplement fixation. This phenomenon may be useful for measuring the in vivo effectiveness of tumoricidal therapy on nonaccessible tumors.
Two new monoclonal antibodies, Lym-1 and Lym-2, reactive with human B-lymphocytes and derived tumors, with immunodiagnostic and immunotherapeutic potential. (1987)

Two new monoclonal antibodies (Lym-1 and Lym-2), reactive with the cell surface of B-lymphocytes and derived tumors, have been produced using tumor cell nuclei preparations as immunogens. Specificity screens using live cell radioimmunoassay techniques with 52 well-characterized human lymphoma and leukemia cell lines showed that both Lym-1 and Lym-2 bound to cell lines of B-cell lineage but were unreactive with those of T-cell, myeloid, or erythroid derivation. The B-cell specificity of these reagents was confirmed on 36 lymphoma and 15 leukemia biopsy specimens by using immunoperoxidase or immunofluorescence techniques. Additionally, flow cytometric analysis of 22 lymphoma biopsies showed that the majority of B-cell tumors were Lym-1 and/or Lym-2 positive and that within a given biopsy, a high percentage of the malignant cell population was stained. In both the immunoperoxidase and flow cytometric studies, reactive T-cells or T-cell lymphomas were consistently negative with the exception of Hodgkin's disease tissues which, in some instances, showed a higher than expected positivity with Lym-1 and Lym-2. Approximately 40% of B-cell chronic lymphocytic leukemias were found to be positive with Lym-1 while 80% were positive with Lym-2. Immunoperoxidase staining of frozen sections of human lymphoid tissues showed that both Lym-1 and Lym-2 stained germinal center and mantle zone B-lymphocytes as well as interfollicular histiocytes. Flow cytometric analysis of normal peripheral blood demonstrated specific staining of B-cells which comprised approximately 8% of circulating lymphocytes. Immunoperoxidase staining of nonlymphoid human organs and tissues revealed weak reactivity of Lym-1 with surface colonic epithelium only. Consistent with these findings, 35 solid tumor cell lines of diverse nature were found unreactive with both Lym-1 and Lym-2. Although standard techniques have thus far failed to identify the antigen recognized by Lym-2, the membrane antigen which binds Lym-1 has been shown by immunoprecipitation and competitive radioimmunoassay studies to be a polymorphic variant of the HLA-Dr antigen. Solid-phase radioimmunoassay techniques have shown that the antigens recognized by Lym-1 and Lym-2 are not significantly modulated after antibody exposure nor shed into the circulation of lymphoma patients. Finally, using iodine-125 labeled preparations of purified Lym-1 and Lym-2, we have determined that both reagents have a relatively large number of antibody binding sites per tumor cell and increased avidity for lymphoma cells when compared to normal and reactive lymph node B-cells.(ABSTRACT TRUNCATED AT 400 WORDS)
CELLULAR IMMUNOABSORPTION USING MONOCLONAL ANTIBODIES (1984)

T cells can be selectively removed from human peripheral blood and bone marrow by passage over a column containing monoclonal anti-T-cell antibodies covalently attached to Sepharose 6MB gel. Effective depletion of T cells from peripheral blood mononuclear cells (PBMC) resulted in the appearance of Leu-2-positive cells, most of which do not express Leu-1 or Leu-4 antigens. Using a column containing anti-Leu-1 or anti-Leu-4 attached to Sepharose 6MB gel, depletion of 98.3% and 99% of T cells from bone marrow mononuclear cells (BMMC), respectively, was demonstrated with recovery of approximately 75% of non-T cells. These columns removed 92.3-98.4% T cells from PBMC with 43.5-74.8% recovery of non-T cells. Combining anti-Leu-1 and anti-Leu-4 antibodies on the same gel removed all detectable T cells from PBMC and BMMC. Proliferative responses to the T cell mitogen, phytohemagglutinin, were abolished from both PBMC and BMMC after column treatment. Preservation of hematopoietic progenitors was observed after treatment of bone marrow, with stem cell recovery averaging 83 +/- 26% for burst-forming units (erythroid), 86 +/- 14% for granulocyte-macrophage progenitors and 94 +/- 16% for granulocyte, erythroid macrophage, and megakaryocitic elements. These results suggest that clinical application of cellular immunoabsorption techniques using monoclonal antibodies will be useful in bone marrow transplantation.
In vitro evaluation of combination drug purging for autologous bone marrow transplantation. (1990)

Using an in vitro model, we studied whether combining 4-hydroperoxycyclophosphamide (4HC) with other drugs could improve its effectiveness as an ex vivo purging agent for autologous bone marrow transplantation. 4HC was incubated simultaneously with vincristine and etoposide, and sequentially with methylprednisolone, in various combinations. Compared to 4HC alone, all drug combinations increased the kill of the leukemia cell lines K562 and CEM without increasing the kill of granulocyte-macrophage colony-forming units (CFU-GM). The combination of 4HC, vincristine and methylprednisolone was the most active, and this drug combination was also the only combination which showed improved selective cytotoxicity (compared to 4HC alone) toward REH cells. This combination inhibited at least 8 logs of clonogenic leukemia cells from all three cell lines at doses which spared 1% of CFU-GM. This was an increase of 1.7 to 6.6 logs of clonogenic leukemia cell kill over 4HC alone. This drug combination displayed similar differential activity between fresh clonogenic leukemia cells and CFU-GM cultured from the bone marrows of seven patients about to undergo autologous bone marrow transplantation for acute lymphocytic leukemia.
Evaluating Differences in Aluminum Exposure through Parenteral Nutrition in Neonatal Morbidities (2017)

Aluminum is a common contaminant in many components of parenteral nutrition, especially calcium and phosphate additives. Although long-term effects have been described in the literature, short-term effects are not well-known. Currently, the Food and Drug Administration recommends maintaining aluminum at &lt;5 mcg/kg/day. This was a single center, retrospective case-control study of 102 neonatal intensive care unit patients. Patients were included if they had a diagnosis of necrotizing enterocolitis, rickets/osteopenia, or seizures and received at least 14 days of parenteral nutrition. Patients were matched 1:1 with control patients by gestational age and birth weight. Mean total aluminum exposure for the 14 days of parenteral nutrition was calculated using manufacturer label information. Differences in mean aluminum exposure between cases and controls, as well as subgroup analysis in those with renal impairment or cholestasis, was conducted. Aluminum exposure in patients meeting inclusion criteria closely mirrored the aluminum exposure of control patients. The difference in aluminum exposure was not found to be statistically significant, except in patients with cholestasis. Although the study found no difference in aluminum exposure in short-term complications with neonates, long-term complications are well established and may warrant the need to monitor and limit neonatal aluminum exposure.
Photocross‐linking of low‐density polyethylene. I. Kinetics and reaction parameters (1993)

Abstract The kinetic characteristics and the reaction conditions of photocross‐linking of low‐density polyethylene (LDPE) in the melt have been studied using benzophenone (BP) and its derivatives such as 4‐chlorobenzophenone (4‐CBP) as photoinitiator and triallyl cyanurate (TAC) as cross‐linker. The efficiency of the photoinitiated cross‐linking system LDPEBP‐TAC and various factors affecting the cross‐linking process, such as photoinitiator and cross‐linker and their concentrations, irradiation time, temperature, and atmosphere, and UV light intensity were examined extensively by determining gel content, IR, and UV spectra. It has been found (i) that LDPE samples of 2–3 mm thickness are easily cross‐linked to a gel content of about 70% with a UV‐irradiation time of about 15 s under optimum conditions; (ii) that the photoinitiating system of a suitable initiator combined with a multifunctional cross‐linker such as 4‐CBP–TAC can enhance the efficiency of photocross‐linking reactions, especially by increasing the initial rate of cross‐linking; (iii) that photocross‐linking of LDPE should be carried out in the melt, which increases the penetration of UV light by decreasing the scattering by crystallites, and (iv) that the rate of cross‐linking is proportional to the square of the light intensity. An increase in light intensity can decrease the concentration of photoinitiator required to reach a certain rate of cross‐linking. The photocross‐linking of polyethylene is promising for industrial applications. © 1993 John Wiley &amp; Sons, Inc.
Identification of disease-specific motifs in the antibody specificity repertoire via next-generation sequencing (2016)

Disease-specific antibodies can serve as highly effective biomarkers but have been identified for only a relatively small number of autoimmune diseases. A method was developed to identify disease-specific binding motifs through integration of bacterial display peptide library screening, next-generation sequencing (NGS) and computational analysis. Antibody specificity repertoires were determined by identifying bound peptide library members for each specimen using cell sorting and performing NGS. A computational algorithm, termed Identifying Motifs Using Next- generation sequencing Experiments (IMUNE), was developed and applied to discover disease- and healthy control-specific motifs. IMUNE performs comprehensive pattern searches, identifies patterns statistically enriched in the disease or control groups and clusters the patterns to generate motifs. Using celiac disease sera as a discovery set, IMUNE identified a consensus motif (QPEQPF[PS]E) with high diagnostic sensitivity and specificity in a validation sera set, in addition to novel motifs. Peptide display and sequencing (Display-Seq) coupled with IMUNE analysis may thus be useful to characterize antibody repertoires and identify disease-specific antibody epitopes and biomarkers.
Biosynthesis of Yersiniabactin, a Complex Polyketide-Nonribosomal Peptide, Using Escherichia coli as a Heterologous Host (2003)

The medicinal value associated with complex polyketide and nonribosomal peptide natural products has prompted biosynthetic schemes dependent upon heterologous microbial hosts. Here we report the successful biosynthesis of yersiniabactin (Ybt), a model polyketide-nonribosomal peptide hybrid natural product, using Escherichia coli as a heterologous host. After introducing the biochemical pathway for Ybt into E. coli, biosynthesis was initially monitored qualitatively by mass spectrometry. Next, production of Ybt was quantified in a high-cell-density fermentation environment with titers reaching 67 +/- 21 (mean +/- standard deviation) mg/liter and a volumetric productivity of 1.1 +/- 0.3 mg/liter-h. This success has implications for basic and applied studies on Ybt biosynthesis and also, more generally, for future production of polyketide, nonribosomal peptide, and mixed polyketide-nonribosomal peptide natural products using E. coli.
Detection of the Philadelphia chromosome in interphase nuclei (1990)

Double fluorescence in situ hybridization was used to detect Philadelphia (Ph) chromosomes in interphase nuclei and metaphases of patients with chronic myeloid leukemia. Application of cosmid probes for 3' ABL and 5' BCR sequences gave better results than libraries for chromosomes 9 and 22. The present approach may provide an alternative method for monitoring minimal residual disease in Ph+ CML patients.
Gene therapy for cancer using tumour-specific prodrug activation. (1994)

Current treatments for metastatic malignant disease are often ineffective. One of the most promising of the selective genetic strategies against cancer is VDEPT (virally directed enzyme prodrug therapy). This uses a viral vector to carry a prodrug-activating enzyme gene into both tumour and normal cells. By linking the foreign gene downstream of tumour-specific transcription units, tumour-specific expression of the foreign enzyme gene can be achieved. We have developed a genetic therapy strategy using VDEPT against cancers that overexpress the oncogene ERBB2. This occurs in approximately one-third of breast and pancreatic tumours (and in a smaller proportion of other tumours) and involves transcriptional up-regulation of the ERBB2 gene with or without gene amplification. We have constructed a chimeric minigene consisting of the proximal ERBB2 promoter linked to the gene encoding cytosine deaminase, an enzyme that can deaminate the prodrug 5-fluorocytosine (5-FC) to form cytotoxic 5-fluorouracil (5-FU). We have constructed a double-copy recombinant retrovirus to deliver the enzyme gene under the control of the ERBB2 promoter into a panel of ERBB2 expression-positive (ERBB2+) and -negative (ERBB2-) pancreatic and breast cell lines. Cytosine deaminase activity was high in ERBB2+ transduced cells but was not detected in ERBB2- transduced cells. Significant cell death was observed in ERBB2+ transduced cells treated with 5-FC whereas ERBB2- cells were not affected. Hence we present a novel gene therapy strategy that is potentially tumour-specific and could be used against a range of tumour types that overexpress the ERBB2 oncogene.
Tumor-Infiltrating CD8+Lymphocytes Predict Clinical Outcome in Breast Cancer (2011)

Breast carcinomas are often infiltrated by inflammatory cells, particularly macrophages and T lymphocytes, but the significance of these cells remains unclear. One possible role of these inflammatory cells is that they represent a cell-mediated immune response against the carcinoma. CD8(+) lymphocytes are a known crucial component of cell-mediated immunity. The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8(+) cytotoxic lymphocytes in breast cancer. Tumor-infiltrating CD8(+) lymphocytes were assessed by immunohistochemical staining of tissue microarray cores from 1,334 unselected breast tumors from patients with long-term follow-up. The number of CD8(+) T cells was counted in tumor nests (intratumoral), in stroma adjacent to tumor cells, and in stroma distant to tumor cells, and their relationship with clinical outcome was determined. The total number of CD8(+) cells was positively correlated with tumor grade (r(s) = 0.20; P < .001) and inversely correlated with patient's age at diagnosis, estrogen receptor-alpha (ER-α), and progesterone receptor (PgR) expression (Mann-Whitney U test, P < .001). The total patient cohort was randomly divided into two separate training and validation sets before performing univariate survival analysis. Total number and distant stromal CD8(+) lymphocytes were associated with better patient survival (P = .041 and P < .001, respectively) in the training set. In multivariate analysis, total CD8(+) T-cell count was an independent prognostic factor in both training and validation sets. These results suggest that tumor-infiltrating CD8(+) T lymphocytes have antitumor activity as judged by their favorable effect on patients' survival and could potentially be exploited in the treatment of breast cancer.
A SIMPLE ALTERNATIVE FOR BEAM RECONFIGURATION OF ARRAY ANTENNAS (2008)

An innovative method for antenna arrays beam configuration is presented. In the proposed method, every element of the array is connected to its feed through a switch, so that it can be active or passive, depending on the switch position. Pattern reconfigurability is achieved by appropriately switching on or off the array elements. The optimal configuration of the switches for each of the radiated patterns, as well the common voltages of the active elements, is calculated by using a genetic algorithm. For each configuration, the currents in the driven and parasitic elements are determined, via their self and mutual impedances, by inversion of the impedance matrix. In the presented examples, the method has been applied to both linear and planar arrays of parallel dipoles that switch the power pattern from a pencil to a flat-topped beam (linear array) or to a footprint pattern (planar array). † Also with University of California, Los Angeles, USA 228 Ares, Franceschetti, and Rodriguez
Layer-by-layer assembly: from conventional to unconventional methods (2006)

Layer-by-layer (LbL) assembly is a powerful means for fabricating multilayer thin films with controlled architecture and composition. This feature article discusses different types of methods for LbL assembly. On the one hand, some of the conventional LbL methods are introduced, which are driven by electrostatic interactions, hydrogen bonds, step-by-step reactions, sol-gel processes, molecular recognition, charge-transfer, stepwise stereocomplex assembly, and electrochemistry. On the other hand, some of the unconventional methods for fabricating of the building blocks which can not be assembled by conventional methods are also summarized. These unconventional methods usually involve the formation of supramolecular structures via one type of self-assembly. These structures can subsequently be used as building blocks in another type of self-assembly. To take advantage of these conventional and unconventional methods, a great number of building blocks can be fabricated into multilayer thin films with a defined sequence structure in a designed way. It has been demonstrated that LbL methods provide new horizons for surface molecular engineering.