gebhart/patrepeval huggingface dataset:
Matrix‐mediated retention of in vitro osteogenic differentiation potential and in vivo bone‐forming capacity by human adult bone marrow‐derived mesenchymal stem cells during ex vivo expansion (2006)

Mesenchymal stem cells (MSCs) represent an attractive cell source for tissue engineering applications, since they are readily isolated from adult bone marrow and have the ability to differentiate along multiple mesenchymal lineages, including osteogenic. Currently, utilization of MSCs for bone tissue engineering is limited because of the attenuation of their osteogenic differentiation potential and in vivo bone-forming capacity following ex vivo expansion on conventional tissue culture plastic (TCP). Previously, we demonstrated that a denatured type I collagen (DC) matrix promotes the maintenance of MSC in vitro osteogenic differentiation potential during ex vivo expansion in contrast to TCP. In this study, we further demonstrate that the maintenance of MSC osteogenic differentiation potential is primarily due to the ability of DC matrix to influence the retention of early passage osteogenic functions in late passage (LP) cells during ex vivo expansion, in contrast to solely enhancing attenuated LP cellular functions during osteogenic differentiation. Serum-associated factors played a significant role in influencing the retention of MSC osteogenic differentiation potential during expansion on the DC matrix. Significantly, the results show that although LP cells expanded ex vivo on TCP highly attentuate their in vivo bone-forming capacity, the expansion of MSCs on DC matrix preserves this ability as determined by histological, histomorphometric, and bone mineral density evaluations of MSC-seeded hydroxyapatite/tricalcium phosphate scaffolds following an 8-week implantation period within a heterotopic muscle pouch model. These findings provide further insight into the importance of matrix-mediated effects on MSC function and selective factors important in this process.
Rapid DNA Chemical Ligation for Amplification of RNA and DNA Signal (2007)

Enzymatic ligation methods are useful in the diagnostic detection of DNA sequences. Here, we describe the investigation of nonenzymatic phosphorothioate--iodoacetyl DNA chemical ligation as a method for the detection and identification of RNA and DNA. The specificity of ligation on the DNA target is shown to allow the discrimination of a single point mutation with a drop in the ligation yield of up to 16.1-fold. Although enzymatic ligation has very low activity for RNA targets, this reaction is very efficient for RNA targets. The speed of the chemical ligation with an RNA target achieves a 70% yield in 5 s, which is equal to or better than that of ligase-enzyme-mediated ligation with a DNA target. The reaction also exhibits a significant level of signal amplification under thermal cycling in periods as short as 100-120 min, with the RNA or DNA target acting in a catalytic way to ligate multiple pairs of probes.
Replacement by Drosophila melanogaster Protamines and Mst77F of Histones during Chromatin Condensation in Late Spermatids and Role of Sesame in the Removal of These Proteins from the Male Pronucleus (2005)

Chromatin condensation is a typical feature of sperm cells. During mammalian spermiogenesis, histones are first replaced by transition proteins and then by protamines, while little is known for Drosophila melanogaster. Here we characterize three genes in the fly genome, Mst35Ba, Mst35Bb, and Mst77F. The results indicate that Mst35Ba and Mst35Bb encode dProtA and dProtB, respectively. These are considerably larger than mammalian protamines, but, as in mammals, both protamines contain typical cysteine/arginine clusters. Mst77F encodes a linker histone-like protein showing significant similarity to mammalian HILS1 protein. ProtamineA-enhanced green fluorescent protein (eGFP), ProtamineB-eGFP, and Mst77F-eGFP carrying Drosophila lines show that these proteins become the important chromosomal protein components of elongating spermatids, and His2AvDGFP vanishes. Mst77F mutants [ms(3)nc3] are characterized by small round nuclei and are sterile as males. These data suggest the major features of chromatin condensation in Drosophila spermatogenesis correspond to those in mammals. During early fertilization steps, the paternal pronucleus still contains protamines and Mst77F but regains a nucleosomal conformation before zygote formation. In eggs laid by sesame-deficient females, the paternal pronucleus remains in a protamine-based chromatin status but Mst77F-eGFP is removed, suggesting that the sesame gene product is essential for removal of protamines while Mst77F removal is independent of Sesame.
Optimistic register coalescing (2004)

Graph-coloring register allocators eliminate copies by coalescing the source and target nodes of a copy if they do not interfere in the interference graph. Coalescing, however, can be harmful to the colorability of the graph because it tends to yield a graph with nodes of higher degrees. Unlike aggressive coalescing , which coalesces any pair of noninterfering copy-related nodes, conservative coalescing or iterated coalescing perform safe coalescing that preserves the colorability. Unfortunately, these heuristics give up coalescing too early, losing many opportunities for coalescing that would turn out to be safe. Moreover, they ignore the fact that coalescing may even improve the colorability of the graph by reducing the degree of neighbor nodes that are interfering with both the source and target nodes being coalesced. This article proposes a new heuristic called optimistic coalescing which optimistically performs aggressive coalescing, thus exploiting the positive impact of coalescing aggressively, but when a coalesced node is to be spilled, it is split back into separate nodes. Since there is a better chance of coloring one of those splits, we can reduce the overall spill amount.
Adenovirus‐Mediated in Vivo Gene Transfer (1994)

Adenovirus vectors are efficient vehicles for in vivo gene transfer to many different cell types. Recombinant adenovirus vectors containing exogenous genes for transfer are derived from adenovirus type 5 and are made replication deficient by the deletion of the E1 region. Based on the observation that many natural adenovirus infections are targeted to airway epithelial cells, a replication-deficient adenovirus vector was constructed containing the cystic fibrosis transmembrane conductance regulator cDNA for the potential therapy of the respiratory manifestations of cystic fibrosis. Using this vector, the normal human CFTR cDNA has been successfully transferred to airway epithelial cells of experimental animals via the trachea. This finding has led to the development of human gene therapy protocols for the evaluation of the safety and efficacy of adenovirus-mediated CFTR cDNA transfer to lungs of individuals with cystic fibrosis. In addition to the airways, adenovirus vectors have been demonstrated to mediate in vivo gene delivery to cells of the liver, blood vessels, brain, muscle, heart, peritoneum, and salivary glands. Adenovirus vectors containing marker genes have also been demonstrated to transfer genes to human tumor cells in nude mice. Such vectors may be useful for a variety of therapeutic applications for in vivo gene transfer for the therapy of cancer and other diseases.
Signaling by the tumor necrosis factor receptor superfamily in B‐cell biology and disease (2011)

Members of the tumor necrosis factor receptor superfamily (TNFRSF) participate prominently in B-cell maturation and function. In particular, B-cell activating factor belonging to the TNF family receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) play critical roles in promoting B-cell survival at distinct stages of development by engaging a proliferation-inducing ligand (APRIL) and/or BAFF. CD40 is also essential for directing the humoral response to T-cell-dependent antigens. Signaling by the TNFRSF is mediated primarily, albeit not exclusively, via the TNFR-associated factor (TRAF) proteins and activation of the canonical and/or non-canonical nuclear factor-κB (NF-κB) pathways. Dysregulated signaling by TNFRSF members can promote B-cell survival and proliferation, causing autoimmunity and neoplasia. In this review, we present a current understanding of the functions of and distinctions between APRIL/BAFF signaling by their respective receptors expressed on particular B-cell subsets. These findings are compared and contrasted with CD40 signaling, which employs similar signaling conduits to achieve distinct cellular outcomes in the context of the germinal center response. We also underscore how new findings and conceptual insights into TNFRSF signaling are facilitating the understanding of B-cell malignancies and autoimmune diseases.
From Facial Parts Responses to Face Detection: A Deep Learning Approach (2015)

In this paper, we propose a novel deep convolutional network (DCN) that achieves outstanding performance on FDDB, PASCAL Face, and AFW. Specifically, our method achieves a high recall rate of 90.99% on the challenging FDDB benchmark, outperforming the state-of-the-art method [23] by a large margin of 2.91%. Importantly, we consider finding faces from a new perspective through scoring facial parts responses by their spatial structure and arrangement. The scoring mechanism is carefully formulated considering challenging cases where faces are only partially visible. This consideration allows our network to detect faces under severe occlusion and unconstrained pose variation, which are the main difficulty and bottleneck of most existing face detection approaches. We show that despite the use of DCN, our network can achieve practical runtime speed.
Solid State RMS Recording Ammeter (1973)

The ammeter described in this paper is essentially a resistor with a variable cross section and a reversible temperature indicator. It has a foil cut into the shape of a double taper with the narrow ends joined at the center of the foil. Current flow through the foil causes a temperature gradient with the higher temperatures in the center. Liquid crystal material coated on the foil substrate changes color reversibly over a discrete range. A narrow color band forms and moves on the taper. The location of the color band is shown to be linearly proportional to the rms current passing through the foil. With the use of irreversible temperature sensing materials, this device will record the peak rms current. The analysis, experimental verification, and design data are presented. In addition, the advantages and disadvantages of this ammeter are described.
The mammalian homologues of frog Bv8 are mainly expressed in spermatocytes (1999)

Bv8, a protein from skin secretions of Bombina variegata, reacts with receptors present in mammalian brain and intestine (Mollay et al. (1999) Eur. J. Pharmacol. 374, 189-196). As deduced from cloned cDNAs, the murine and human Bv8 homologues have identical amino-terminal sequences and also contain 10 cysteines. From mouse testes, two forms of Bv8 mRNA have been characterized, of which one contains an additional exon which codes for 21 mostly basic amino acids. The mouse Bv8 gene is most active in mid-late pachytene spermatocytes. In mouse testes, Bv8 mRNA can first be detected at the end of the second week post partum.
Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a. (1994)

Glycogen storage disease (GSD) type 1a is an autosomal recessive inborn error of metabolism caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Southern blot hybridization analysis using a panel of human-hamster hybrids showed that human G6Pase is a single-copy gene located on chromosome 17. To correlate specific defects with clinical manifestations of this disorder, we identified mutations in the G6Pase gene of GSD type 1a patients. In the G6Pase gene of a compound heterozygous patient (LLP), two mutations in exon 2 of one allele and exon 5 of the other allele were identified. The exon 2 mutation converts an arginine at codon 83 to a cysteine (R83C). This mutation, previously identified by us in another GSD type 1a patient, was shown to have no detectable phosphohydrolase activity. The exon 5 mutation in the G6Pase gene of LLP converts a glutamine codon at 347 to a stop (Q347SP). This Q347SP mutation was also detected in all exon 5 subclones (five for each patient) of two homozygous patients, KB and CB, siblings of the same parents. The predicted Q347SP mutant G6Pase is a truncated protein of 346 amino acids, 11 amino acids shorter than the wild type G6Pase of 357 residues. Site-directed mutagenesis and transient expression assays demonstrated that G6Pase-Q347SP was devoid of G6Pase activity. G6Pase is an endoplasmic reticulum (ER) membrane-associated protein containing an ER retention signal, two lysines (KK), located at residues 354 and 355. We showed that the G6Pase-K355SP mutant containing a lysine-355 to stop codon mutation is enzymatically active. Our data demonstrate that the ER protein retention signal in human G6Pase is not essential for activity. However, residues 347-354 may be required for optimal G6Pase catalysis.
Limitations of HLA‐transgenic mice in presentation of HLA‐restricted cytotoxic T‐cell epitopes from endogenously processed human papillomavirus type 16 E7 protein (2002)

We investigated the use of mice transgenic for human leucocyte antigen (HLA) A*0201 antigen-binding domains to test vaccines composed of defined HLA A*0201-restricted cytotoxic T-lymphocyte (CTL) epitopes of human papillomavirus (HPV) type 16 E7 oncoprotein. HPV is detected in >90% of cervical carcinomas. HPV16 E7 oncoprotein transforms cells of the uterine cervix and functions as a tumour-associated antigen to which immunotherapeutic strategies may be directed. We report that although the HLA A*0201 E7 epitope peptides function both to prime for E7 CTL responses, and to sensitize target cells for E7-directed CTL killing in situations where antigen processing is not required, the epitopes are not processed out of either endogenously expressed or immunization-introduced E7, by the mouse antigen-processing and presentation machinery. Thus (1) CTL induced by HLA A*0201 peptide immunization killed E7 peptide-pulsed target cells, but did not kill target cells expressing whole E7; (2) immunization with whole E7 protein did not elicit CTL directed to HLA A*0201-restricted E7 CTL epitopes; (3) HLA A*0201-restricted CTL epitopes expressed in the context of a DNA polytope vaccine did not activate E7-specific T cells either in 'conventional' HLA A*0201 transgenic (A2.1Kb) mice, or in HHD transgenic mice in which expression of endogenous H-2 class 1 is precluded; and (4) HLA A*0201 E7 peptide epitope immunization was incapable of preventing the growth of an HLA A*0201- and E7-expressing tumour. There are generic implications for the universal applicability of HLA-class 1 transgenic mice for studies of human CTL epitope presentation in murine models of human infectious disease where recognition of endogenously processed antigen is necessary. There are also specific implications for the use of HLA A2 transgenic mice for the development of E7-based therapeutic vaccines for cervical cancer.
Smad Signaling Is Required to Maintain Epigenetic Silencing during Breast Cancer Progression (2010)

Breast cancer progression is associated with aberrant DNA methylation and expression of genes that control the epithelial-mesenchymal transition (EMT), a critical step in malignant conversion. Although the genes affected have been studied, there is little understanding of how aberrant activation of the DNA methylation machinery itself occurs. Using a breast cancer cell-based model system, we found that cells that underwent EMT exhibited overactive transforming growth factor beta (TGFbeta) signaling and loss of expression of the CDH1, CGN, CLDN4, and KLK10 genes as a result of hypermethylation of their corresponding promoter regions. Based on these observations, we hypothesized that activated TGFbeta-Smad signaling provides an "epigenetic memory" to maintain silencing of critical genes. In support of this hypothesis, disrupting Smad signaling in mesenchymal breast cancer cells resulted in DNA demethylation and reexpression of the genes identified. This epigenetic reversal was accompanied by an acquisition of epithelial morphology and a suppression of invasive properties. Notably, disrupting TGFbeta signaling decreased the DNA binding activity of DNA methyltransferase DNMT1, suggesting that failure to maintain methylation of newly synthesized DNA was the likely cause of DNA demethylation. Together, our findings reveal a hyperactive TGFbeta-TGFbetaR-Smad2 signaling axis needed to maintain epigenetic silencing of critical EMT genes and breast cancer progression.
Reliability-based hybrid ARQ (2002)

A new hybrid automatic repeat request (ARQ) scheme that utilises reliability estimates generated by soft-input, soft-output (SISO) decoders is proposed. The proposed ARQ scheme transmits additional information for the unreliable bits, and this information is used to perform additional decoding. Results are presented that show this ARQ technique can provide performance close to the channel capacity.
Folate, Vitamin B12, and Homocysteine as Risk Factors for Cognitive Decline in the Elderly (2008)

These results suggest that folate and homocysteine are involved in the etiology of cognitive decline in the elderly.
A new consistent model explaining structure (conformation)-activity relationships of opiates with mu-selectivity. (1993)

Several different classes of opiates such as PET (7-alpha-(1-Hydroxy-1-methyl-3-phenylpropyl)-6,14-endo-ethenotetra - hydronorthebaine), phenazocine, fentanyl, carfentanil, ohmefentanyl, prodine derivatives, methadone and etonitazene have been investigated using the molecular modelling program package SYBYL and the TRIPOS empirical force field. Comparison of the energetically optimized structures and their corresponding molecular electrostatic potentials was used for the development of a new model of conformation-activity relationships of mu-selective opiates. We considered six important spatial positions of these molecules which were assumed to be directly implicated in the interaction with the opiate receptor. We found that these opiates may bind to the receptor with their protonated nitrogen atom assuming one or the other of two different orientations. The obtained results offer new insights into important receptor interactions and the diverse opiate activities of all the compounds examined can be explained in a unified manner. For example, the most active ohmefentanyl stereo-isomer was predicted on the basis of the proposed model.
New Antimicrobial Agents for Gram-positive Infections * (2001)

Increasing antimicrobial resistance in Gram-positive bacteria has presented a formidable treatment problem. The enterococci, although traditionally non-virulent pathogens, have been shown, when associated with vancomycin resistance, to have an attributable mortality of approximately 40%. The frightening specter of widespread vancomycin resistance in the more virulent Staphylococcus aureus would have a significantly greater impact. Since the late 1980s, advances have been made in the development of pharmacological weapons against multiply resistant Gram-positive bacterial infections. At least seven new antimicrobial classes that have activity against resistant Gram-positive organisms are in various stages of development. Most are semisynthetic derivatives of known antibiotics; however, importantly, a unique class of antimicrobial agent has also emerged.
CAMPATH-1H (Cambridge University). (1999)

CAMPATH-1H, a T-cell-depleting, humanized monoclonal antibody, is under development by LeukoSite and ILEX for the potential treatment of chronic lymphocytic leukemia (CLL). In August 1998, ILEX completed enrollment of a pivotal clinical trial of CAMPATH-1H in the treatment of CLL. The study has enrolled 94 patients at 20 centers in the US and Europe. It is anticipated that achievement of the target response would result in a biologics license application being filed with the FDA in mid-1999. Preliminary unaudited results reported by one of the clinical sites were positive. Additional potential therapeutic areas include vasculitis and multiple sclerosis. Preliminary studies have also shown the antibody may reverse acute renal transplant rejection episodes and be useful in ex vivo purging of bone marrow to remove potentially malignant cells. The US FDA has granted Fast Track designation to CAMPATH. The product has orphan drug status.
Tumor markers in staging and prognosis of colorectal carcinoma. (2008)

The precise preoperative staging of colorectal cancer is fundamental for surgical strategy, incomplete staging means incomplete treatment and poor outcome. Large-scale clinical evaluations of predictive markers are currently in progress, including determination of their ability to predict response of patients to therapy for advanced disease and for adjuvant treatment. Lack of specificity and sensitivity preclude the use of all existing serum markers for the early detection of colorectal carcinoma. The aim of the study was to investigate the clinical significance of serum tumor markers and biological activity markers -- oncofetal tumormarker CEA, mucin tumormarkers CA19-9, CA242, proliferative tumor markers Thymidine kinase, soluble cytoceratines fragments TPS, TPA, adhesive molecules ICAM - 1, VCAM -1, IGF-1, and adipocytokinins Adiponectin, Leptin in patients with colorectal cancer before primary operation. The study included 142 patients between the ages of 35 - 89 years. Operated between November 2003 to March 2006. We have confirmed that CA19-9 is besides CEA an important marker in colorectal cancer. Comparing CA19-9 and CA242 in preoperative staging, CA242 is more specific. Statistical significant difference between early and metastatic stage of colorectal cancer was not confirmed in markers: ICAM-1, VCAM, adiponectin, leptin. Statistical significant difference between early and metastatic stage of colorectal cancer was confirmed in markers: CEA, CA19-9, CA242, TPS, TPA, TK, IGF-1. None of the used markers was able to distinguish stage II and III, in other words to identify patients with infiltration of lymph nodes. This fact is very important in our aspirations to find which marker from periferal blood could help to poit out patients in risk of lymphatic infiltration and to indicate these patients for adjuvant therapy. Combination of CEA and either CA19-9 or CA242 can be recommended for preoperative investigation. CA 242 in this study seems to have slightly better results in preoperative staging.
Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients (2010)

The findings suggest that DBS can suppress pathological 11-30 Hz activity in the vicinity of stimulation in patients with Parkinson's disease. This suppression occurs at stimulation voltages that are clinically effective.