gebhart/patrepeval huggingface dataset:
Strategies and clinical outcome of 250 cycles of Preimplantation Genetic Diagnosis for single gene disorders (2005)

Minisequencing for mutation detection combined with multiplex fluorescence PCR for linkage analysis is an efficient, accurate and widely applicable strategy for PGD of SGDs. Our experience provides a further demonstration that PGD is an effective clinical tool and a useful option for many couples with a high risk of transmitting a genetic disease.
Differential uptake and cross-presentation of human papillomavirus virus-like particles by dendritic cells and Langerhans cells. (2003)

A causal link between cervical cancer and high-risk human papillomaviruses has been established. The virus infects basal cells of the mucosa, where Langerhans cells are the resident antigen-presenting cells. Langerhans cells and dendritic cells, which are targeted by vaccination, internalize similar amounts of human papillomavirus virus-like particles (VLPs), albeit through different uptake mechanisms. VLP uptake by dendritic cells results in activation and cross-presentation of MHC class I-restricted peptides with costimulation to T cells. Conversely, VLP uptake by Langerhans cells leads to cross-presentation in the absence of costimulation. Efficient VLP cross-presentation by Langerhans cells with costimulation can be achieved by addition of CD40 ligand. The lack of a protective immune response after viral contact with Langerhans cells may explain why some women fail to mount an immune response against the virus or why the immune responses that do develop may allow the virus to persist. Because VLPs are currently being tested as a vaccine against cervical cancer, our data are very topical and have implications for optimal vaccination strategies against this disease.
Poly (DL‐lactide‐co‐glycolide) (PLGA) Nanoparticles with Entrapped  trans ‐Cinnamaldehyde and Eugenol for Antimicrobial Delivery Applications (2011)

Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design smart food systems for future delivery applications, including packaging and processing, capable of ensuring food safety to consumers.
Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans (2003)

IgG is the most abundant serum antibody and is an essential component of the humoral immune response. It is known that the 'neonatal' Fc receptor (FcRn) plays a role in maintaining constant serum IgG levels by acting as a protective receptor which binds and salvages IgG from degradation. However, the cellular mechanism that is involved in serum IgG homeostasis is poorly understood. In the current study we address this issue by analyzing the intracellular fate in human endothelial cells of IgG molecules which bind with different affinities to FcRn. The studies show that IgG which do not bind to FcRn accumulate in the lysosomal pathway, providing a cellular explanation for short serum persistence of such antibodies. We have also investigated the saturability of the homeostatic system and find that it has limited capacity. Our observations have direct relevance to the understanding and treatment of IgG deficiency, and to the effective application of therapeutic antibodies.
Canonical and non‐canonical wnts differentially affect the development potential of primary isolate of human bone marrow mesenchymal stem cells (2007)

This study examines the role of Wnt signaling events in regulating the differential potential of mesenchymal stem cells (MSCs) from adult bone marrow (BM). Immunohistochemical analysis of BM revealed co-localization of Wnt5a protein, a non-canonical Wnt, with CD45(+) cells and CD45(-) STRO-1(+) cells, while Wnt3a expression, a canonical Wnt, was associated with the underlying stroma matrix, suggesting that Wnts may regulate MSCs in their niche in BM. To elucidate the role of Wnts in MSC development, adult human BM-derived mononuclear cells were maintained as suspension cultures to recapitulate the marrow cellular environment, in serum-free, with the addition of Wnt3a and Wnt5a protein. Results showed that Wnt3a increased cell numbers and expanded the pool of MSCs capable of colony forming unit -- fibroblast (CFU-F) and CFU -- osteoblast (O), while Wnt5a maintained cell numbers and CFU-F and CFU-O numbers. However, when cells were cultured directly onto tissue culture plastic, Wnt5a increased the number of CFU-O relative to control conditions. These findings suggest the potential dual role of Wnt5a in the maintenance of MSCs in BM and enhancing osteogenesis ex vivo. Our work provides evidence that Wnts can function as mesenchymal regulatory factors by providing instructive cues for the recruitment, maintenance, and differentiation of MSCs.
Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease (1996)

The ribonucleotide reductase (RR) of herpes simplex virus type 1 (HSV-1) is an important virulence factor, being required for neurovirulence, ocular virulence, and reactivation from latency. The RR activity requires the association of two distinct homodimeric subunits, and the association of the subunits is inhibited in the presence of a peptide homologous to the carboxy terminus of the small subunit. A structural analog of the inhibitory peptide (BILD 1263) has been shown to inhibit the replication of HSV-1 at micromolar concentrations in vitro. We used a mouse model of HSV-1 ocular infection to determine the in vivo efficacy of topical BILD 1263. Treatment of HSV-1 KOS-infected mice resulted in significant reductions in the severity and incidence of stromal keratitis and corneal neovascularization. At higher concentrations (5%) BILD 1263 reduced the severity but not the incidence of blepharitis. Treatment with 5% BILD 1263 also reduced viral shedding from the cornea by 10- to 14-fold (P < 0.001). In uninfected mice treated with 5% BILD 1263, we found no evidence of corneal epithelial damage, conjunctivitis, or blepharitis, and histopathological studies revealed no changes in the corneas of these mice. These results show that the peptidomimetic RR inhibitor BILD 1263 is effective in preventing disease, has an antiviral effect in vivo, and has little or no toxicity.
Complete Sequence and Genomic Analysis of Rhesus Cytomegalovirus (2003)

The complete DNA sequence of rhesus cytomegalovirus (RhCMV) strain 68-1 was determined with the whole-genome shotgun approach on virion DNA. The RhCMV genome is 221,459 bp in length and possesses a 49% G+C base composition. The genome contains 230 potential open reading frames (ORFs) of 100 or more codons that are arranged colinearly with counterparts of previously sequenced betaherpesviruses such as human cytomegalovirus (HCMV). Of the 230 RhCMV ORFs, 138 (60%) are homologous to known HCMV proteins. The conserved ORFs include the structural, replicative, and transcriptional regulatory proteins, immune evasion elements, G protein-coupled receptors, and immunoglobulin homologues. Interestingly, the RhCMV genome also contains sequences with homology to cyclooxygenase-2, an enzyme associated with inflammatory processes. Closer examination identified a series of candidate exons with the capacity to encode a full-length cyclooxygenase-2 protein. Counterparts of cyclooxygenase-2 have not been found in other sequenced herpesviruses. The availability of the complete RhCMV sequence along with the ability to grow RhCMV in vitro will facilitate the construction of recombinant viral strains for identifying viral determinants of CMV pathogenicity in the experimentally infected rhesus macaque and to the development of CMV as a vaccine vector.
Identification and Analysis of Over 2000 Ribosomal Protein Pseudogenes in the Human Genome (2002)

Mammals have 79 ribosomal proteins (RP). Using a systematic procedure based on sequence-homology, we have comprehensively identified pseudogenes of these proteins in the human genome. Our assignments are available at http://www.pseudogene.org or http://bioinfo.mbb.yale.edu/genome/pseudogene. In total, we found 2090 processed pseudogenes and 16 duplications of RP genes. In relation to the matching parent protein, each of the processed pseudogenes has an average relative sequence length of 97% and an average sequence identity of 76%. A small number (258) of them do not contain obvious disablements (stop codons or frameshifts) and, therefore, could be mistaken as functional genes, and 178 are disrupted by one or more repetitive elements. On average, processed pseudogenes have a longer truncation at the 5' end than the 3' end, consistent with the target-primed-reverse-transcription (TPRT) mechanism. Interestingly, on chromosome 16, an RPL26 processed pseudogene was found in the intron region of a functional RPS2 gene. The large-scale distribution of RP pseudogenes throughout the genome appears to result, chiefly, from random insertions with the numbers on each chromosome, consequently, proportional to its size. In contrast to RP genes, the RP pseudogenes have the highest density in GC-intermediate regions (41%-46%) of the genome, with the density pattern being between that of LINEs and Alus. This can be explained by a negative selection theory as we observed that GC-rich RP pseudogenes decay faster in GC-poor regions. Also, we observed a correlation between the number of processed pseudogenes and the GC content of the associated functional gene, i.e., relatively GC-poor RPs have more processed pseudogenes. This ranges from 145 pseudogenes for RPL21 down to 3 pseudogenes for RPL14. We were able to date the RP pseudogenes based on their sequence divergence from present-day RP genes, finding an age distribution similar to that for Alus. The distribution is consistent with a decline in retrotransposition activity in the hominid lineage during the last 40 Myr. We discuss the implications for retrotransposon stability and genome dynamics based on these new findings.
Repeat Expansion Detection (RED) and the RED Cloning Strategy (2003)

Trinucleotide repeat sequences are present at approx 30,000-40,000 loci in the human genome (1). The majority of these repeats are below 35 copies and are stably transmitted. However, unstable trinucleotide repeat expansions at some loci have been found to be the causal mutation for nearly 20 genetic neurodegenerative disorders in human (2–4). Most of these disorders occur at repeat lengths above 35 copies, with a tendency towards further expansion upon successive transmissions. An inverse correlation between the repeat length and disease severity/earlier age of onset, known as anticipation, has been observed in most of the families transmitting such types of diseases, suggesting that the length change of the repeats may play a role in the manifestation of anticipation. Only three motifs, CAG/CTG, CGG/CCG, and GAA/TTC, of the 10 possible trinucleotide repeat permutations have so far been associated with human disease. It remains possible that other disease phenotypes are caused by expansions of any repeat motif at any repeat containing locus. We have established a repeat detection and gene-isolation system, which allows identification of a repeat-containing gene within a couple of months.
Treatment of Severe Combined Immunodeficiency Disease (SCID) due to Adenosine Deaminase Deficiency with CD34 + Selected Autologous Peripheral Blood Cells Transduced with a Human ADA Gene (Amendment). National Institutes of Health (1993)

Significant increases in lymphocyte adenosine deaminase activity, T cell numbers and immune function have been achieved in the two children with SCID thus far treated with autologous T cells genetically-corrected by retroviral-mediated insertion of a normal ADA gene. Although the data obtained to date demonstrate that the use of ADA gene corrected peripheral T cells appears to be an effective treatment for ADA(-)SCID, it is theoretically preferable to try to develop a treatment for these children that will result in stem cell gene correction. The genetic correction of T cell progenitors with long-term immune reconstituting ability would be more desirable because repeated infusions of genetically altered cells should not be necessary and the generation of a more complete repertoire of T cell specificities might also be possible. Furthermore, the present treatment protocol involves indefinite continuation of enzyme replacement treatment with PEG-ADA. The demonstration of ADA gene expression in the progeny of transduced stem cells may simplify the decision concerning cessation of this very costly enzyme treatment (approximately $250,000/yr./patient). Recent evidence suggests that a small fraction of bone marrow or peripheral blood mononuclear cells bearing the CD34 antigen contains hematopoietic stem cells with both lymphoid and myeloid reconstituting ability. We propose in this amendment to supplement the infusion of human ADA gene-transduced autologous T cells in children with ADA(-)SCID with autologous peripheral blood CD34+ cells transduced with a second, readily distinguishable ADA vector.(ABSTRACT TRUNCATED AT 250 WORDS)
Planar waveguide-coupled, high-index-contrast, high-Q resonators in chalcogenide glass for sensing (2008)

High-index-contrast compact microdisk resonators in thermally evaporated As2S3 and Ge17Sb12S71 chalcogenide glass films are designed and fabricated using standard UV lithography and characterized. Our pulley coupler configuration demonstrates coupling of the resonators to monolithically integrated photonic wire waveguides without resorting to demanding fine-line lithography. Microdisk resonators in As2S3 support whispering-gallery-mode with cavity quality factors (Q) exceeding 2 x 10(5), the highest Q value reported in resonator structures in chalcogenide glasses to the best of our knowledge. We have successfully demonstrated a lab-on-a-chip prototype sensor device with the integration of our resonator with planar microfluidic systems. The sensor shows a refractive index sensitivity of 182 nm/RIU (refractive index unit) and a wavelength resolution of 0.1 pm through a resonant peak fit. This corresponds to a refractive index detection limit of 8 x 10(-7) RIU at 1550 nm in wavelength, which could be further improved by shifting the operating wavelength to a region where water absorption is reduced.
Diagnosis and epidemiology of Clostridium difficile enterocolitis in Sweden (1984)

Experience of the diagnosis and epidemiology of Clostridium difficile in Sweden is reviewed. Samples from 5885 patients have been investigated at the National Bacteriological Laboratory in Stockholm from 1978-1983. Patients originate from all parts of the country and their number continues to increase. Cl. difficile seem to be of growing importance, especially in nosocomial infections. Most patients with antibiotic-associated diarrhoea and colitis (AAD/AAC) and Cl. difficile in their stools were above 60 years of age (63%) and there was a significant preponderance of females over males in the age groups 21-50 and above 60 years of age. The antibiotics most commonly associated with Cl. difficile enterocolitis (CDE) were penicillins, cephalosporins and clindamycin/lincomycin. On the basis of consumption clindamycin/lincomycin and cephalosporins are associated 70 and 40 times, respectively, more often than penicillins in CDE. Diagnosis of CDE relies mainly on detection of the cytotoxin (toxin B) in stool specimens. It was present in 873/4793 (18.2%) patients whereas the bacterium was found in only 12%. An immunoassay for detection of the enterotoxin (toxin A) of Cl. difficile seems to be a useful alternative to the cytotoxin assay, but some stool specimens with a low toxin B titre were negative. Five specimens negative for toxin B were positive for toxin A and came from patients where additional information suggested CDE. A serological assay for demonstration of circulating antibodies to Cl. difficile toxins has also been evaluated and is positive in about half of the cases of CDE. Antibody response seems to be absent or delayed in patients with relapse of colitis after antibiotic treatment.
Rate Acceleration of Anionic Oxy‐Cope Rearrangements Induced by an Additional Unsaturation. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Dominant Tolerance to Kidney Allografts Induced by Anti-Donor MHC Class II Antibodies: Cooperation between T and Non-T CD103+ Cells (2006)

Allograft acceptance can be induced in the rat by pretransplant infusion of donor blood or spleen cells. Although promoting long-term acceptance, this treatment is also associated with chronic rejection. In this study, we show that a single administration of anti-donor MHC class II alloimmune serum on the day of transplantation results in indefinite survival of a MHC-mismatched kidney graft. Long-term recipients accept a donor-type skin graft and display no histological evidence of chronic rejection. The kidney grafts of tolerant animals display an accumulation of TCR Cbeta, FoxP3, and IDO transcripts. Moreover, as compared with syngeneic recipients, tolerant recipients harbor a large infiltrate of MHC class II(+) cells and CD103(+) cells. In vitro, splenocytes from tolerant recipients exhibit decreased donor-specific proliferation, which is restored by depletion of non-T cells and partially restored by the blockade of IDO. Finally, splenocytes from tolerant recipients, but not purified T cell splenocytes, transfer donor-specific infectious tolerance without chronic rejection, after infusion into naive recipients, over two generations. However, splenocytes depleted of T cells or splenocytes depleted of CD103(+) cells fail to transfer tolerance. Collectively, these data show that a single administration of anti-donor MHC class II alloimmune serum induces a tolerant state characterized by an infiltration of the kidney graft by regulatory T cells and CD103(+) cells. These data also show that the transfer of tolerance requires the presence of both T cells and CD103(+) dendritic cells. The precise mechanism of cooperation of these two cell subsets remains to be defined.
Interleaved memory function interpolators with application to an accurate LNS arithmetic unit (1994)

This paper describes a new method for polynomial interpolation in hardware, with advantages demonstrated by its application to an accurate logarithmic number system (LNS) arithmetic unit. The use of an interleaved memory reduces storage requirements by allowing each stored function value to be used in interpolation across several segments. This strategy can be shown to always use fewer words of memory than an optimized polynomial with stored polynomial coefficients. Interleaved memory function interpolators are then applied to the specific goal of an accurate logarithmic number system arithmetic unit. Many accuracy requirements for the LNS arithmetic unit are possible. Although a round to nearest would be desirable, it cannot be easily achieved. The goal suggested is to insure that the worst case LNS relative error is smaller than the worst case floating point (FP) relative error. Using the interleaved memory interpolator, the detailed design of an LNS arithmetic unit is performed using a second order polynomial interpolator including approximately 91K bits of ROM. This arithmetic unit has better accuracy and less complexity than previous LNS units.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Diastolic Dysfunction in Normotensive Men with Well-Controlled Type 2 Diabetes (2001)

LVDD is much more common than previously reported in subjects with well-controlled type 2 diabetes who are free of clinically detectable heart disease. The high prevalence of this phenomenon in this high-risk population suggests that screening for LVDD in type 2 diabetes should include procedures such as the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of ventricular filling.
The Physiologic Replacement of Insulin (1989)

ALTHOUGH insulin was discovered and first administered more than 65 years ago,1 , 2 the goal of physiologic replacement remains elusive, despite major advances in our understanding of insulin's physiologic effects, chemistry, kinetics, and action. In this article I shall evaluate the pharmacologic features and use of insulin in the context of current practices in the management of insulin-dependent diabetes mellitus.As background, it will be useful to review briefly the physiology of insulin synthesis and secretion.3 Insulin is synthesized in the beta cells of the islets of Langerhans as a single polypeptide precursor, preproinsulin, which is subsequently converted to proinsulin, an . . .
Induction of the CTLA-4 Gene in Human Lymphocytes Is Dependent on NFAT Binding the Proximal Promoter (2007)

CTLA-4 is a member of the costimulatory family, has homology to CD28, and binds the B7 family of ligands. Unlike CD28, CTLA-4 ligation transmits a negative signal in T cells. CTLA-4 expression, while inducible in most T cells, is expressed constitutively on T cells with a regulatory phenotype. The mechanism controlling CTLA-4 expression in human T cells is poorly characterized, thus we sought to better understand the mechanism of activation of the CTLA-4 gene. By cloning the 5' upstream promoter and creating promoter-deletion reporter constructs, we show that the proximal promoter is critical for activating the CTLA-4 gene. Within this region, we identify a NFAT consensus sequence that binds NFAT with high affinity that differs from other NFAT sequences and does not recruit AP-1. Analysis of the chromatin proteins in the native CTLA-4 gene shows that this promoter region becomes associated with acetylated histones by chromatin immunoprecipitation assays. In addition, NFAT1 binds to the promoter of the CTLA-4 gene after stimulation by chromatin immunoprecipitation. The functional requirement of the NFAT site for CTLA-4 transcription was demonstrated by mutations in the NFAT site that abolished the activity of the promoter. Furthermore, inhibitors of NFAT suppressed CTLA-4 gene expression, indicating that NFAT plays a critical role in regulating the induction of the CTLA-4 gene in lymphocytes. The identification of NFAT as a critical regulator of the CTLA-4 gene suggests that targeting NFAT function may lead to novel approaches to modulate the CTLA-4 gene to control the immune response.
Research progress in motor neuron diseases. (1988)

The cause of amyotrophic lateral sclerosis is not known. However, there is increasing evidence that the syndrome has more than one cause. Many of the different categories of causation are dealt with in the papers presented in this symposium - including genetic and acquired forms, and multiple categories within those two major classes. The diversity of different causes gives hope that progress in one field will be followed by elucidation of other fields. As examples, there has been progress in understanding the genetic forms due to hexosaminidase deficiency and molecular genetics is being applied to other heritable motor neuron diseases. Among acquired diseases, in different parts of the world, there has been new evidence that persistent viral infection may be important, that dietary constituents may be important, and that paraproteinemia may be important.