gebhart/patrepeval huggingface dataset:
Immunological Aspects of Haploidentical Stem Cell Transplantation in Children (2001)

Thirty-eight children with high-risk hematological malignancies underwent transplantation with megadoses of peripheral mobilized CD34+ cells from haploidentical parents (n = 24) or from matched unrelated donors (n = 14). The CD34+ cells were isolated to a purity of > 98% using magnetic-activated cell sorting. This high purity was associated with an almost complete depletion of T lymphocytes. No pharmacological prophylaxis for graft-versus-host disease (GvHD) was used, and significant primary GvHD was not seen. A final engraftment was seen in all patients. Sixteen patients are alive and disease-free with a median follow-up of 24 months. The immunological reconstitution was faster in the patients transplanted with CD34+ stem cells from the haploidentical donors compared to the matched unrelated donors, and the transplantation of large numbers of haploidentical CD34+ stem cells seems to be superior to that of the matched unrelated donors. The phenotypical and functional analysis of the immune reconstitution provided some insights into the biology of transplantation of highly purified CD34+ cells. In this article, we summarize our current results with the transplantation of highly purified stem cells and discuss possible implications for further antileukemic post-transplant therapeutic strategies.
An End-to-End Compression Framework Based on Convolutional Neural Networks (2017)

Summary form only given. Traditional image coding standards (such as JPEG and JPEG2000) make the decoded image suffer from many blocking artifacts or noises since the use of big quantization steps. To overcome this problem, we proposed an end-to-end compression framework based on two CNNs, as shown in Figure 1, which produce a compact representation for encoding using a third party coding standard and reconstruct the decoded image, respectively. To make two CNNs effectively collaborate, we develop a unified end-to-end learning framework to simultaneously learn CrCNN and ReCNN such that the compact representation obtained by CrCNN preserves the structural information of the image, which facilitates to accurately reconstruct the decoded image using ReCNN and also makes the proposed compression framework compatible with existing image coding standards.
Noncollinearly Phase-Matched Second Harmonic Generation in Stilbene-Dye-Attached Polymer Thin Films (1989)

Noncollinearly phase-matched second harmonic generation (SHG) of Nd:YAG-laser light (1.064 µm) has been measured in a thin-film waveguide of stilbene-dye substituted methacrylate polymer on a glass substrate. The second-order nonlinear optical coefficient d 33 of the corona-poled film is 1.6×10 -8 esu (at 1.064 µm). The phase-matching crossing angle of two guided fundamental beams is about 3.6° in the 1.38±0.02 µm-thick polymer waveguide. The SHG efficiency has been estimated to be about 5×10 -5 % for the fundamental peak power of about 130 W. The broad angular dependence of SH power has resulted from the short interaction length (0.1∼1 mm order) of two fundamental beams.
Generation of knockout rabbits using transcription activator-like effector nucleases (2014)

Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platforms contributing to redefine the boundaries of modern biological research. They are composed of a non-specific cleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications by inducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases have been employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively. This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies, biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbits using transcription activator-like effector nucleases, and a perspective of the field.
Approved monoclonal antibodies for cancer therapy (2008)

An overview of the FDA approved monoclonal antibodies is provided. Monoclonal antibodies are currently used as the standard of care as first and second line therapy for a number of hematologic malignancies and solid tumors. Over the next 5 - 10 years additional monoclonal antibodies and monoclonal antibody conjugates will be approved by the US FDA and will dramatically affect the standard of care of many cancers.
Pharmacokinetics of Curcumin Conjugate Metabolites in Healthy Human Subjects (2008)

Curcumin is absorbed after oral dosing in humans and can be detected as glucuronide and sulfate conjugates in plasma.
A miniature integrated device for automated multistep genetic assays (2000)

A highly integrated monolithic device was developed that automatically carries out a complex series of molecular processes on multiple samples. The device is capable of extracting and concentrating nucleic acids from milliliter aqueous samples and performing microliter chemical amplification, serial enzymatic reactions, metering, mixing and nucleic acid hybridization. The device, which is smaller than a credit card, can manipulate over 10 reagents in more than 60 sequential operations and was tested for the detection of mutations in a 1.6 kb region of the HIV genome from serum samples containing as few as 500 copies of the RNA. The elements in this device are readily linked into complex, flexible and highly parallel analysis networks for high throughput sample preparation or, conversely, for low cost portable DNA analysis instruments in point-of-care medical diagnostics, environmental testing and defensive biological agent detection.
Anti-CD20/CD3 T cell–dependent bispecific antibody for the treatment of B cell malignancies (2015)

Bispecific antibodies and antibody fragments in various formats have been explored as a means to recruit cytolytic T cells to kill tumor cells. Encouraging clinical data have been reported with molecules such as the anti-CD19/CD3 bispecific T cell engager (BiTE) blinatumomab. However, the clinical use of many reported T cell-recruiting bispecific modalities is limited by liabilities including unfavorable pharmacokinetics, potential immunogenicity, and manufacturing challenges. We describe a B cell-targeting anti-CD20/CD3 T cell-dependent bispecific antibody (CD20-TDB), which is a full-length, humanized immunoglobulin G1 molecule with near-native antibody architecture constructed using "knobs-into-holes" technology. CD20-TDB is highly active in killing CD20-expressing B cells, including primary patient leukemia and lymphoma cells both in vitro and in vivo. In cynomolgus monkeys, CD20-TDB potently depletes B cells in peripheral blood and lymphoid tissues at a single dose of 1 mg/kg while demonstrating pharmacokinetic properties similar to those of conventional monoclonal antibodies. CD20-TDB also exhibits activity in vitro and in vivo in the presence of competing CD20-targeting antibodies. These data provide rationale for the clinical testing of CD20-TDB for the treatment of CD20-expressing B cell malignancies.
Per-antenna Constant Envelope Precoding for Large Multi-User MIMO Systems (2012)

We consider the multi-user MIMO broadcast channel with $M$ single-antenna users and $N$ transmit antennas under the constraint that each antenna emits signals having constant envelope (CE). The motivation for this is that CE signals facilitate the use of power-efficient RF power amplifiers. Analytical and numerical results show that, under certain mild conditions on the channel gains, for a fixed $M$, array gain is achievable even under the stringent per-antenna CE constraint (essentially, for a fixed $M$, at sufficiently large $N$ the total transmitted power can be reduced with increasing $N$ while maintaining a fixed information rate to each user). Simulations for the i.i.d. Rayleigh fading channel show that the total transmit power can be reduced linearly with increasing $N$ (i.e., an O(N) array gain). We also propose a precoding scheme which finds near-optimal CE signals to be transmitted, and has O(MN) complexity. Also, in terms of the total transmit power required to achieve a fixed desired information sum-rate, despite the stringent per-antenna CE constraint, the proposed CE precoding scheme performs close to the sum-capacity achieving scheme for an average-only total transmit power constrained channel.
Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. (1993)

Left ventricular hypertrophy (LVH) is associated with reinduction of the fetal program of gene expression. It is unclear whether this pattern of cardiac gene expression changes with the development of left ventricular decompensation and failure. To answer these questions, we quantified steady-state levels of mRNA by the polymerase chain reaction in the left ventricular myocardium of rats 8 and 20 weeks after ascending aortic banding. Clinical and hemodynamic assessment identified two distinct groups of animals 20 weeks after aortic banding. The first group (20-week nonfailed LVH) demonstrated substantial LVH but no depression in systolic developed pressure per gram left ventricular weight compared with the age-matched control group. In contrast, a second group of rats exhibited clinical signs of congestive failure as well as a marked diminution in left ventricular developed pressure per gram. Assessment of the levels of mRNA encoding a panel of cardiac proteins demonstrated a greater than twofold increase in beta-myosin heavy chain mRNA and an approximately sixfold increase in atrial natriuretic factor mRNA in left ventricular myocardium of all three groups (8-week LVH, 20-week nonfailed LVH, 20-week failed LVH) when compared with appropriate age-matched control groups. In contrast, Ca(2+)-ATPase mRNA levels were decreased by 50% only in the left ventricular myocardium of animals with both clinical signs and hemodynamic indexes consistent with cardiac decompensation (20-week failed LVH). These results suggest that in rats with ascending aortic banding the hypertrophic phenotype is associated with a selective reinduction of the fetal gene program, which persists even after the development of left ventricular failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis (2012)

Mesenchymal stem cells (MSCs) have been considered as an attractive tool for the therapy of diseases. Exosomes excreted from MSCs can reduce myocardial ischemia/reperfusion damage and protect against acute tubular injury. However, whether MSC-derived exosomes can relieve liver fibrosis and its mechanism remain unknown. Previous work showed that human umbilical cord-MSCs (hucMSCs) transplanted into acutely injured and fibrotic livers could restore liver function and improve liver fibrosis. In this study, it was found that transplantation of exosomes derived from hucMSC (hucMSC-Ex) reduced the surface fibrous capsules and got their textures soft, alleviated hepatic inflammation and collagen deposition in carbon tetrachloride (CCl4)-induced fibrotic liver. hucMSC-Ex also significantly recovered serum aspartate aminotransferase (AST) activity, decreased collagen type I and III, transforming growth factor (TGF)-β1 and phosphorylation Smad2 expression in vivo. In further experiments, we found that epithelial-to-mesenchymal transition (EMT)-associated markers E-cadherin-positive cells increased and N-cadherin- and vimentin-positive cells decreased after hucMSC-Ex transplantation. Furthermore, the human liver cell line HL7702 underwent typical EMT after induction with recombinant human TGF-β1, and then hucMSC-Ex treatment reversed spindle-shaped and EMT-associated markers expression in vitro. Taken together, these results suggest that hucMSC-Ex could ameliorate CCl4-induced liver fibrosis by inhibiting EMT and protecting hepatocytes. This provides a novel approach for the treatment of fibrotic liver disease.
Distinct Effects of Saturated and Monounsaturated Fatty Acids on β-Cell Turnover and Function (2001)

Glucotoxicity and lipotoxicity contribute to the impaired beta-cell function observed in type 2 diabetes. Here we examine the effect of saturated and unsaturated fatty acids at different glucose concentrations on beta-cell proliferation and apoptosis. Adult rat pancreatic islets were cultured onto plates coated with extracellular matrix derived from bovine corneal endothelial cells. Exposure of islets to saturated fatty acid (0.5 mmol/l palmitic acid) in medium containing 5.5, 11.1, or 33.3 mmol/l glucose for 4 days resulted in a five- to ninefold increase of beta-cell DNA fragmentation. In contrast, monounsaturated palmitoleic acid alone (0.5 mmol/l) or in combination with palmitic acid (0.25 or 0.5 mmol/l each) did not affect DNA fragmentation. Increasing concentrations of glucose promoted beta-cell proliferation that was dramatically reduced by palmitic acid. Palmitoleic acid enhanced the proliferation activity in medium containing 5.5 mmol/l glucose but had no additional effect at higher glucose concentrations (11.1 and 33.3 mmol/l). The cell-permeable ceramide analog C2-ceramide mimicked both the palmitic acid-induced beta-cell apoptosis and decrease in proliferation. Moreover, the ceramide synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on beta-cell viability. Additionally, palmitic acid but not palmitoleic acid decreased the expression of the mitochondrial adenine nucleotide translocator and induced release of cytochrome c from the mitochondria into the cytosol. Finally, palmitoleic acid improved beta-cell-secretory function that was reduced by palmitic acid. Taken together, these results suggest that the lipotoxic effect of the saturated palmitic acid involves an increased apoptosis rate coupled with reduced proliferation capacity of beta-cells and impaired insulin secretion. The deleterious effect of palmitate on beta-cell turnover is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway. In contrast, the monounsaturated palmitoleic acid does not affect beta-cell apoptosis, yet it promotes beta-cell proliferation at low glucose concentrations, counteracting the negative effects of palmitic acid as well as improving beta-cell function.
Advanced functional polymer membranes (2006)

This feature article provides a comprehensive overview on the development of polymeric membranes having advanced or novel functions in the various membrane separation processes for liquid and gaseous mixtures (gas separation, reverse osmosis, pervaporation, nanofiltration, ultrafiltration, microfiltration) and in other important applications of membranes such as biomaterials, catalysis (including fuel cell systems) or lab-on-chip technologies. Important approaches toward this aim include novel processing technologies of polymers for membranes, the synthesis of novel polymers with well-defined structure as ‘designed’ membrane materials, advanced surface functionalizations of membranes, the use of templates for creating ‘tailored’ barrier or surface structures for membranes and the preparation of composite membranes for the synergistic combination of different functions by different (mainly polymeric) materials. Self-assembly of macromolecular structures is one important concept in all of the routes outlined above. These rather diverse approaches are systematically organized and explained by using many examples from the literature and with a particular emphasis on the research of the author's group(s). The structures and functions of these advanced polymer membranes are evaluated with respect to improved or novel performance, and the potential implications of those developments for the future of membrane technology are discussed.
Age-associated memory impairment (1995)

In this issue of Neurology, Koivisto et al [1] present important epidemiologic data on the prevalence of age-associated memory impairment (AAMI). As originally defined, AAMI represents persons aged 50 or older who have a subjective sense of decline in memory relative to their younger adult years, perform at least 1 SD below the mean for young adults on standard measures of memory function, are not demented, and have no other medical or psychiatric condition that can account for this memory decline [2]. Koivisto et al [1] discuss other issues concerning this controversial diagnostic category that merit further discussion, particularly since a related modified diagnostic category, Age-Related Cognitive Decline, has been included in DSM-IV [3].

Previous reports on the epidemiology of AAMI have not employed the specific diagnostic criteria for AAMI and have utilized varying methodology [4,5] or have been based on archival data reported for age-associated normative data on standard memory tests [6]. Koivisto et al [1] are the first to apply the specific AAMI criteria in a random, large-scale epidemiologic study, and they report a prevalence rate for AAMI of 38.4%, which declined with age, based on 1,049 subjects aged 60 to 78 years.

Their study [1] addresses several issues concerning the concept of AAMI: its relation to normal aging and Alzheimer's disease (AD); whether it has value as a diagnostic entity; and the utility of the objective memory tests, subjective complaints, intellectual capacity testing, and dementia exclusion factors proposed in the original definition of AAMI [2].

Koivisto et al [1] view AAMI as a phenomenon of normal aging and rate their reported prevalence of 38.4% as high. However, the data in their table 3 show that 8.8% of 1,049 subjects, or 92, had dementia, as defined by a Mini-Mental State Examination (MMSE) score of …
Immunochemical cross-reactivity between cyanogen bromide fragments of human serum albumin. (1982)

The antigenic structure of human albumin was investigated in order to establish whether or not there was any similarity between its antigenic sites. Using immunoadsorbent columns prepared with cyanogen bromide fragments of human serum albumin, antibodies directed against different portions of the albumin molecules were isolated. Measurement of the amount of the antibodies isolated and study of their specificity by inhibition techniques show that these subpopulations of antibodies reacted not only with the fragment used for their isolation (homologous) but also with the other fragments (heterologous). Heterologous fragments were inhibiting only at a very high concentration with regard to the homologous ones. These results show that there is a weak cross-reactivity between different portions of the albumin molecule. This reaction is most probably due to the homology existing in the sequence of the human albumin molecule which has arisen by gene duplication. The same type of behavior can be predicted to extent to other molecules which have evolved by similar mechanisms.
Dendritic cells and the pathogenesis of rheumatoid arthritis (1999)

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which unknown arthrogenic autoantigen is presented to CD4+ T cells. The strong association of the disease with an epitope within the HLA-DR chain shared between various alleles of HLA-DR4 and DR1 emphasizes the importance of antigen presentation. This immune response predominantly occurs in the synovial tissue and fluid of the joints and autoreactive T cells are readily demonstrable in both the synovial compartment and blood. Circulating dendritic cells (DC) are phenotypically and functionally identical with normal peripheral blood (PB) DC. In the synovial tissue, fully differentiated perivascular DC are found in close association with T cells and with B cell follicles, sometimes containing follicular DC. These perivascular DC migrate across the activated endothelium from blood and receive differentiative signals within the joint from monocyte-derived cytokines and CD40-ligand+ T cells. In the SF, DC manifest an intermediate phenotype, similar to that of monocyte-derived DC in vitro. Like a delayed-type hypersensitivity response, the rheumatoid synovium represents an effector site. DC at many effector sites have a characteristic pattern of infiltration and differentiation. It is important to note that the effector response is not self-limiting in RA autoimmune inflammation. In this article, we argue that the presentation of self-antigen by DC and by autoantibody-producing B cells is critical for the perpetuation of the autoimmune response. Permanently arresting this ongoing immune response with either pharmaceutical agents or immunotherapy is a major challenge for immunology.
Automated microparticle enzyme immunoassay for neural thread protein in cerebrospinal fluid from alzheimer's disease patients (1992)

An automated microparticle enzyme immunoassay (MEIA) with the IMx analyzer for the detection of neural thread protein (NTP) in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients was developed. This assay uses monoclonal antibodies produced against the purified pancreatic form of the protein. The assay employs one monoclonal antibody covalently coupled to the microparticle to capture immunoreactive material in CSF or brain tissue. The second monoclonal antibody was conjugated to alkaline phosphatase and serves as detection antibody. The assay provides results in approximately 45 minutes with a sensitivity of 60 pg/ml (3 fmoles/ml). The titration curve of both normal and AD CSF resulted in a linear relationship with respect to the volume of CSF used. A similar relationship was observed when normal and AD brain tissue extracts were serially diluted. The molecular weight of NTP in CSF was approximately 20 kD as determined by gel filtration method under non-denaturing conditions. The recovery for pancreatic thread protein (PTP) spiked in either normal or AD CSF was 104% and 108%, respectively. Intra-, inter-, and total assay CVs (coefficient of variation) for controls were less than 2.9%, 3.3% and 3.0%, respectively. This assay will provide a useful tool in the study of the Alzheimer's disease and may help research in diagnosis and prognosis of Alzheimer's disease and related disorders.
γ-Interferon Signaling in Pancreatic β-Cells Is Persistent but Can Be Terminated by Overexpression of Suppressor of Cytokine Signaling-1 (2001)

Proinflammatory cytokines, including gamma-interferon (IFN-gamma), have been implicated in the destruction of beta-cells in autoimmune diabetes. IFN-gamma signaling is transient in some cell types, but there is indirect evidence that it may be prolonged in beta-cells. In this study, we have shown that IFN-gamma signaling, measured by signal transducer and activator of transcription-1 (STAT1) activation and the expression of IFN-gamma-responsive genes, is persistent in beta-cells for as long as the cytokine is present. Because members of the suppressor of cytokine signaling (SOCS) family may regulate the duration of IFN-gamma signaling, their expression was investigated in beta-cells. We found that cytokine-inducible SH2-containing protein, SOCS-1, and SOCS-2 are expressed in primary islets and NIT-1 insulinoma cells, both at the mRNA and protein levels, after treatment with IFN-gamma and other proinflammatory cytokines. Transfected SOCS-1 was found to inhibit responses to IFN-gamma in NIT-1 insulinoma cells, including STAT1 activation, class I major histocompatibility complex upregulation, and IFN-gamma-induced cell death, but only when expressed at levels higher than those found in untransfected cells. Consistent with this, IFN-gamma signaling was not affected in SOCS-1-deficient beta-cells. Therefore, persistent IFN-gamma signaling in beta-cells is associated with SOCS-1 expression that is not sufficient to terminate signaling. Because overexpression of SOCS-1 can suppress responses to IFN-gamma, this may be a useful strategy for protecting beta-cells from cytotoxicity mediated by IFN-gamma and possibly other proinflammatory cytokines.