gebhart/patrepeval huggingface dataset:
Synthesis of a nonacosapeptide (β‐fragment) corresponding to the N‐terminal sequence 1–29 of human liver metallothionein II and its heavy metal‐binding properties (1985)

A nonacosapeptide (beta-fragment) corresponding to the N-terminal sequence 1-29 of human liver metallothionein II was synthesized by the fragment condensation method. The Cd-binding ability of the beta-fragment was much stronger than that of cysteine as thionein and synthetic alpha-fragment corresponding to the C-terminal sequence 30-61 of human liver metallothionein II. Both the alpha- and beta-fragments bound preferentially to Cu ions rather than Cd ions.
YPEL3, a p53-Regulated Gene that Induces Cellular Senescence (2010)

Cellular senescence, the limited ability of cultured normal cells to divide, can result from cellular damage triggered through oncogene activation (premature senescence) or the loss of telomeres following successive rounds of DNA replication (replicative senescence). Although both processes require a functional p53 signaling pathway, relevant downstream p53 targets have been difficult to identify. Discovery of senescence activators is important because induction of tumor cell senescence may represent a therapeutic approach for the treatment of cancer. In microarray studies in which p53 was reactivated in MCF7 cells, we discovered that Yippee-like-3 (YPEL3), a member of a recently discovered family of putative zinc finger motif coding genes consisting of YPEL1-5, is a p53-regulated gene. YPEL3 expression induced by DNA damage leads to p53 recruitment to a cis-acting DNA response element located near the human YPEL3 promoter. Physiologic induction of YPEL3 results in a substantial decrease in cell viability associated with an increase in cellular senescence. Through the use of RNAi and H-ras induction of cellular senescence, we show that YPEL3 activates cellular senescence downstream of p53. Consistent with its growth suppressive activity, YPEL3 gene expression is repressed in ovarian tumor samples. One mechanism of YPEL3 downregulation in ovarian tumor cell lines seems to be hypermethylation of a CpG island upstream of the YPEL3 promoter. We believe these findings point to YPEL3 being a novel tumor suppressor, which upon induction triggers a permanent growth arrest in human tumor and normal cells.
Epilepsy in four genetically determined syndromes of intellectual disability (2011)

The annotation highlights research describing disturbances in excitatory and inhibitory neurotransmitter systems, neuronal ion channel and glial functions that provide possible explanations for the co-occurrence of seizures within several ID syndromes, in some cases suggesting possible avenues for research into novel therapeutic targets. Phenotypic overlaps between syndromes may also relate to roles for the implicated genes in different disturbances in linked biochemical pathways.
A pig‐to‐mouse coronary artery transplantation model for investigating the pathogenicity of anti‐pig antibody (2015)

This study provides the first direct in vivo comparison of the pathogenicity of naive human and baboon serum. The results suggest that human preformed non-Gal antibody may have increased pathogenicity compared to baboon. This model, which showed a rejected graft histopathology similar to antibody-mediated rejection in cardiac xenotransplantation, may be useful to assess the pathogenicity of individual protein or carbohydrate specific non-Gal reactive antibodies.
Dual recognition of a human cytotoxic T-cell clone for melanoma antigens. (1996)

It is well known that tumor-specific CTLs have a crucial role in the elimination of tumors and that different CTL populations recognize tumor antigens in MHC-restricted and MHC-unrestricted manners. We have established two alpha beta CTL clones that recognize melanoma antigens in both human lymphocyte antigen (HLA)-A2-restricted and HLA-unrestricted manners. Flow cytometry analysis showed that these CTL clones carry CD3, CD8, and alpha beta T-cell receptor (TCR) and express low levels of CD56. In contrast, these CTL clones do not express CD16, indicating that they do not contain natural killer cells. TCR analysis of these CTL clones using an anchored PCR method revealed that each clone carries a single alpha beta TCR. Both CTL clones contained the same Valpha and Vbeta gene segments although they carried different Jalpha and Jbeta gene segments. Taken together, these results confirm that CTL clones that carry a single alpha beta TCR recognize melanoma antigens in both HLA-A2-restricted and HLA-unrestricted manners. It is strongly suggested that the dual recognition of these CTL clones for the melanoma antigens is mediated by TCRs. The novel mechanism for antitumor immunity by these CTLs may be important in the effective elimination of tumors in vivo.
Overview on electrostatic discharge protection designs for mixed-voltage I/O interfaces: design concept and circuit implementations (2006)

Electrostatic discharge (ESD) protection design for mixed-voltage I/O interfaces has been one of the key challenges of system-on-a-chip (SOC) implementation in nano-scale CMOS processes. The on-chip ESD protection circuit for mixed-voltage I/O interfaces should meet the gate-oxide reliability constraints and prevent the undesired leakage current paths. This paper presents an overview on the design concept and circuit implementations of the ESD protection designs for mixed-voltage I/O interfaces without using the additional thick gate-oxide process. The ESD design constraints in mixed-voltage I/O interfaces, the classification and analysis of ESD protection designs for mixed-voltage I/O interfaces, and the designs of high-voltage-tolerant power-rail ESD clamp circuit are presented and discussed.
Digital TV multiprogramme by satellite - converging to a world wide standard (1997)

There is an increasing world wide interest in the introduction of satellite digital multiprogramme television. ITU-R BO 1211 Recommendation recommends the consideration of a digital multiprogramme television system, along with other digital existing systems, in converging towards a world wide standard. In consequence, the ITU decided in 1995 to appoint a Special Rapporteur to prepare a report on common elements, definition of interfaces, etc. among the various satellite digital multiprogramme TV systems operating at 11/12 Ghz. The work done by the Special Rapporteur has concluded on the most useful way to converge to a world wide standard for satellite digital multiprogramme. This way consist in defining the Common Functional Requirements of the Universal Elements of a common Integrated Receiver Decoder (Set-top-box) in a new ITU-R Recommendation. This paper presents the details of the recommended performances to be met by the universal elements of the common functional requirements of a satellite Integrated Receiver Decoder. The universal elements of a satellite set-top-box perform the following functions: demodulation and decoding, transport and demultiplexing as well as source decoding of video, audio and data. The incorporation of these elements into a single set-top-box allows the processing of signals independently of the format used in the transmission: either DVB-S, DSS or GI-MPEG2. Future activities are now being addressed to the set-top-box upgrading it with interactive capabilities as well as to the exploration of convergence for the other additional essential functions (as interfaces, EPG, SI, etc.)
Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain. (1995)

We cloned a novel ankyrin, Ank3, from mouse kidney cDNA. The full-length transcript is predicted to encode a 214-kD protein containing an 89 kD, NH2 terminal "repeat" domain; a 65 kD, central "spectrin-binding" domain; and a 56 kD, COOH-terminal "regulatory" domain. The Ank3 gene maps to mouse Chromosome 10, approximately 36 cM from the centromere, a locus distinct from Ank1 and Ank2. Ank3 is the major kidney ankyrin. Multiple transcripts of approximately 7.5, 6.9, 6.3, 5.7, 5.1, and 4.6 kb are highly expressed in kidney where Ank1 and Ank2 mRNAs are barely detectable. The smaller mRNAs (< or = 6.3 kb) lack the entire repeat domain. These transcripts have a unique 5'untranslated region and NH2-terminal sequence and encode a predicted protein of 121 kD. Two small sequences of 21 and 18 amino acids are alternatively spliced at the junction of the repeat and spectrin-binding domains in the larger (> or = 6.9 kb) RNAs. Alternative splicing of a 588 bp sequence (corresponding to a 21.5-kD acidic amino acid sequence) within the regulatory domain also occurs. Ank3 is much more widely expressed than previously described ankyrins. By Northern hybridization or immunocytochemistry, it is present in most epithelial cells, in neuronal axons, in muscle cells, and in megakaryocytes/platelets, macrophages, and the interstitial cells of Leydig (testis). On immunoblots, an antibody raised to a unique regions of the regulatory domain detects multiple Ank3 isoforms in the kidney (215, 200, 170, 120, 105 kD) and in other tissues. The 215/200 kD and 120/105-kD kidney proteins are close to the sizes predicted for the 7.5/6.9- and 6.3/5.7-kb RNAs (with/without the 588-bp acidic insert). Interestingly, it appears that Ank3 exhibits a polarized distribution only in tissues that express the approximately 7.0-kb isoforms, the only isoforms in the kidney that contain the repeat domain. In tissues where smaller transcripts (< or = 6.3 kb) are expressed. Ank3 is diffusely distributed in some or all cells and may be associated with cytoplasmic structures. We conclude that Ank3 is a broadly distributed epithelial ankyrin and is the major ankyrin in the kidney and other tissues, where it plays an important role in the polarized distribution of many integral membrane proteins.
A neurocontroller based on model feedback and the adaptive heuristic critic (1990)

A neurocontroller is presented which seeks to minimize a reinforcement signal presented to the controller over time. The architecture is based on P.J. Werbos's (1989) backpropagated critic and incorporates A.G. Barto and R.S. Sutton's (1983) adaptive heuristic critic. Preliminary experiments performed with the cart-pole problem indicate that the method is faster, yet more unstable than a comparable method. The performance is significantly enhanced when a simple proportional control loop is used in conjunction with the neurocontroller
Chitosan tubes of varying degrees of acetylation for bridging peripheral nerve defects (2013)

Biosynthetic nerve grafts are desired as alternative to autologous nerve grafts in peripheral nerve reconstruction. Artificial nerve conduits still have their limitations and are not widely accepted in the clinical setting. Here we report an analysis of fine-tuned chitosan tubes used to reconstruct 10 mm nerve defects in the adult rat. The chitosan tubes displayed low, medium and high degrees of acetylation (DAI: ≈ 2%, DA: ≈ 5%, DAIII: ≈ 20%) and therefore different degradability and microenvironments for the regenerating nerve tissue. Short and long term investigations were performed demonstrating that the chitosan tubes allowed functional and morphological nerve regeneration similar to autologous nerve grafts. Irrespective of the DA growth factor regulation demonstrated to be the same as in controls. Analyses of stereological parameters as well as the immunological tissue response at the implantation site and in the regenerated nerves, revealed that DAI and DAIII chitosan tubes displayed some limitations in the support of axonal regeneration and a high speed of degradation accompanied with low mechanical stability, respectively. The chitosan tubes combine several pre-requisites for a clinical acceptance and DAII chitosan tubes have to be judged as the most supportive for peripheral nerve regeneration.
A Nonsense Mutation in a Cinnamyl Alcohol Dehydrogenase Gene Is Responsible for the Sorghum <i>brown midrib6</i> Phenotype   (2009)

Brown midrib6 (bmr6) affects phenylpropanoid metabolism, resulting in reduced lignin concentrations and altered lignin composition in sorghum (Sorghum bicolor). Recently, bmr6 plants were shown to have limited cinnamyl alcohol dehydrogenase activity (CAD; EC 1.1.1.195), the enzyme that catalyzes the conversion of hydroxycinnamoyl aldehydes (monolignals) to monolignols. A candidate gene approach was taken to identify Bmr6. Two CAD genes (Sb02g024190 and Sb04g005950) were identified in the sorghum genome based on similarity to known CAD genes and through DNA sequencing a nonsense mutation was discovered in Sb04g005950 that results in a truncated protein lacking the NADPH-binding and C-terminal catalytic domains. Immunoblotting confirmed that the Bmr6 protein was absent in protein extracts from bmr6 plants. Phylogenetic analysis indicated that Bmr6 is a member of an evolutionarily conserved group of CAD proteins, which function in lignin biosynthesis. In addition, Bmr6 is distinct from the other CAD-like proteins in sorghum, including SbCAD4 (Sb02g024190). Although both Bmr6 and SbCAD4 are expressed in sorghum internodes, an examination of enzymatic activity of recombinant Bmr6 and SbCAD4 showed that Bmr6 had 1 to 2 orders of magnitude greater activity for monolignol substrates. Modeling of Bmr6 and SbCAD4 protein structures showed differences in the amino acid composition of the active site that could explain the difference in enzyme activity. These differences include His-57, which is unique to Bmr6 and other grass CADs. In summary, Bmr6 encodes the major CAD protein involved in lignin synthesis in sorghum, and the bmr6 mutant is a null allele.
Synthesis of Mesoporous Silica Coated Magnetic Microspheres on Large Scale (2011)

We present a simple method to synthesize the mesoporous Fe 3 O 4 @SiO 2 via two-step procedure on large scale, and CTAB plays dual role in the sol-gel reaction. First it can prevent the Fe 3 O 4 from depositing, ensure to obtain silica homogenouly coated Fe 3 O 4 . What’s more important, it also act as the template to synthesize the mesoporous Fe 3 O 4 @SiO 2 . In addition, the mesoporous Fe 3 O 4 @SiO 2 will be potential in application of bioseparation.
Noise calibrator for v.h.f. and u.h.f. field-strength-measuring receivers (1967)

A simple noise generator, based on a semiconductor diode of the Zener type and suitable for use in the frequency range 30–900 MHz, can be used to check both absolute gain and noise performance of sensitive receivers.
Applications of fluorescence in situ hybridization (FISH) in detecting genetic aberrations of medical significance (2010)

Fluorescence in situ hybridization (FISH) is a powerful technique used in the detection of chromosomal abnormalities. The high sensitivity and specificity of FISH and the speed with which the assays can be performed have made FISH a pivotal cytogenetic technique that has provided significant advances in both the research and diagnosis of haematological malignancies and solid tumours. From a medical perspective, FISH can be applied to detect genetic abnormalities such as characteristic gene fusions, aneuploidy, loss of a chromosomal region or a whole chromosome or to monitor the progression of an aberration serving as a technique that can help in both the diagnosis of a genetic disease or suggesting prognostic outcomes. FISH can also be applied to such research applications as gene mapping or the identification of novel oncogenes or genetic aberrations that contribute towards various cancers. FISH is based on DNA probes annealing to specific target sequence of sample DNA. Attached to the probes are fluorescent reporter molecules which under fluorescence microscopy confirm the presence or absence of a particular genetic aberration when viewed under fluorescence microscopy. The technique has recently evolved to allow screening of the whole genome simultaneously through multicolour whole-chromosome probe techniques such as multiplex FISH or spectral karyotyping, or through an array-based method using comparative genomic hybridization. This simple, yet effective, technique has revolutionized cytogenetics and has become well established in its potential as a diagnostic and discovery tool in the fight against cancer.
R&D challenges and solutions for highly complex distributed systems: a middleware perspective (2011)

Abstract Highly complex distributed systems (HCDSs) are characterized by a large number of mission-critical, heterogeneous inter-dependent subsystems executing concurrently with diverse—often conflicting—quality-of-service (QoS) requirements. Creating, integrating, and assuring these properties in HCDSs is hard and expecting application developers to perform these activities without significant support is unrealistic. As a result, the computing and communication foundation for HCDSs is increasingly based on middleware. This article examines key R&D challenges that impede the ability of researchers and developers to manage HCDS software complexity. For each challenge that must be addressed to support HCDSs, the article surveys the state-of-the-art middleware solutions to these challenges and describes open issues and promising future research directions.
Low-molecular-weight GTP-binding proteins and leukocyte signal transduction (1995)

Recent progress on the understanding of leukocyte signal transduction pathways indicates that many of these pathways are modulated by low-molecular-weight GTP-binding proteins (LMWGs). LMWGs are members of a growing family of GTP-binding proteins known as the Ras superfamily and act as molecular switches for regulating a wide range of signal-transduction pathways in virtually all cells. In leukocytes, LMWGs have been shown to participate in essential cellular functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemoattractant-induced signaling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, phospholipid metabolism, and intracellular vesicle transport and secretion, and many more of these functions will certainly be identified as we gain a further understanding of regulatory pathways modulating leukocyte signal transduction. This review will summarize our current understanding of this rapidly advancing area of research.
<sup>18</sup>F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging (2008)

Dual integrin alpha(v)beta(3) and GRPR recognition showed significantly improved tumor-targeting efficacy and pharmacokinetics compared with (18)F-labeled RGD and BBN analogs. The same heterodimeric ligand design may also be applicable to other receptor system combinations and other imaging modalities.
Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1‐year Phase 1/2 clinical trial (2019)

Pegunigalsidase alfa, a novel PEGylated, covalently crosslinked form of α-galactosidase A developed as enzyme replacement therapy (ERT) for Fabry disease (FD), was designed to increase plasma half-life and reduce immunogenicity, thereby enhancing efficacy compared with available products. Symptomatic adults with FD participated in this open-label, 3-month dose-ranging study, followed by a 9-month extension. Three cohorts were enrolled in a stepwise manner, each receiving increased doses of pegunigalsidase alfa: 0.2, 1.0, 2.0 mg/kg, via intravenous infusion every other week. Pharmacokinetic analysis occurred on Day 1 and Months 3, 6, and 12. Kidney biopsies at baseline and Month 6 assessed peritubular capillary globotriaosylceramide (Gb3) content. Renal function, cardiac parameters, and other clinical endpoints were assessed throughout. Treatment-emergent adverse events (AEs) and presence of immunoglobulin G (IgG) antidrug antibodies (ADAs) were assessed. Sixteen patients completed 1 year's treatment. Mean terminal plasma half-life (each cohort) ranged from 53 to 121 hours. All 11 male and 1 of 7 female patients presented with classic FD phenotype, in whom renal peritubular capillary Gb3 inclusions were reduced by 84%. Mean estimated glomerular filtration rate was 111 mL/min/1.73 m<sup>2</sup> at baseline, remaining stable throughout treatment. Three patients developed treatment-induced IgG ADAs; following 1 year's treatment, all became ADA-negative. Nearly all treatment-emergent AEs were mild or moderate. One patient withdrew from the study following a serious related AE. Pegunigalsidase alfa may represent an advance in ERT for FD, based on its unique pharmacokinetics and apparent low immunogenicity.
5′-Nucleotide phosphodiesterase isozyme-V as a marker for liver metastases in breast cancer patients (1984)

A 2-year prospective study testing 258 breast cancer patients for the presence of 5'-nucleotide phosphodiesterase isozyme-V (5'-NPD-V) as a marker for liver metastases was undertaken. Despite the difficulty associated with such a study in obtaining data from biopsy (only 12 patients) and autopsy (only 18 patients), the 5'-NPD-V test correctly predicted confirmed liver metastases in 39 of 41 patients (95%). Of this group, 25 patients had abnormal liver scans at the time the 5'-NPD-V test was positive (64%). In 11 of 39 patients 5'-NPD-V was found positive before liver scans. In the majority of patients, 5'-NPD-V fluctuated between positive and negative during follow-up. While such transiently positive values may be related to treatment, they should be interpreted conservatively as liver proliferation until confirmed otherwise. Throughout the 2-year study only seven patients with nonmalignant hepatic diseases had consistent positive values (2.7%). As an indicator of liver metastases 5'-NPD-V is more specific than other liver function tests. It is also important to note that 14 patients received early chemotherapy because attention was directed toward the diagnosis of liver metastases by this test.
In Vitro Fluorescence Anisotropy Analysis of the Interaction of Full-length SRC1a with Estrogen Receptors α and β Supports an Active Displacement Model for Coregulator Utilization (2006)

Binding of full-length P160 coactivators to hormone response element-steroid receptor complexes has been difficult to investigate in vitro. Here, we report a new application of our recently described fluorescence anisotropy microplate assay to investigate binding and dissociation of full-length steroid receptor coactivator-1a (SRC1a) from full-length estrogen receptor alpha (ERalpha) or estrogen receptor beta (ERbeta) bound to a fluorescein-labeled (fl) estrogen response element (ERE). SRC1a exhibited slightly higher affinity binding to flERE.ERbeta than to flERE.ERalpha. Binding of SRC1a to flERE.ERalpha and to flERE.ERbeta was 17beta-estradiol (E2)-dependent and was nearly absent when ICI 182,780, raloxifene, or 4-hydroxytamoxifen were bound to the ERs. SRC1a binds to flERE.E2-ERalpha and flERE.E2-ERbeta complexes with a t1/2 of 15-20 s. Short LXXLL-containing nuclear receptor (NR) box peptides from P160 coactivators competed much better for SRC1a binding to flERE.E2-ER than an NR box peptide from TRAP220. However, approximately 40-250-fold molar excess of the P160 NR box peptides was required to inhibit SRC1a binding by 50%. This suggests that whereas the NR box region is a primary site of interaction between SRC1a and ERE.E2-ER, additional contacts between the coactivator and the ligand-receptor-DNA complex make substantial contributions to overall affinity. Increasing amounts of NR box peptides greatly enhanced the rate of dissociation of SRC1a from preformed flERE.E2-ER complexes. The data support a model in which coactivator exchange is facilitated by active displacement and is not simply the result of passive dissociation and replacement. It also shows that an isolated coactivator exhibits an inherent capacity for rapid exchange.