gebhart/patrepeval huggingface dataset:
Vertical ridge augmentation by means of deproteinized bovine bone block and recombinant human platelet-derived growth factor-BB: a histologic study in a dog model. (2006)

The primary objective of this proof-of-principle study was to evaluate the outcome of vertical ridge augmentation in a standardized dog model by combining purified recombinant platelet-derived growth factor (rhPDGF-BB) and a block of deproteinized cancellous bovine bone. The secondary objective was to determine the value of a resorbable barrier membrane to improve the efficacy of the procedure. Six adult foxhounds were committed to bilateral surgical extraction of all four mandibular premolars. A vertical alveolar ridge defect was created at the time of the extractions. Three months later, the artificially created defects were grafted: Group A used a deproteinized bovine bone block in combination with a collagen barrier membrane, group B used a deproteinized bovine bone block infused with rhPDGF-BB only, and group C included a deproteinized bovine bone block infused with rhPDGF-BB, plus a collagen resorbable barrier membrane. After 4 months, the animals were sacrificed. Histologic examination of group B revealed a large amount of newly formed bone, and a large amount of bone-to-implant contact was visible in the areas of bone regeneration extending over the top of the implant cover screw. The results of this preclinical canine study provide proof-of-principle that rhPDGF-BB, used in combination with a deproteinized bovine block without placement of a barrier membrane, has the potential to regenerate significant amounts of new bone in severe mandibular ridge defects. In addition, the results seem to point to the importance of the periosteum as a source of osteoprogenitor cells in growth factor-mediated regenerative procedures.
On the ecological and evolutionary significance of storage in clonal plants (1999)

Environmental heterogeneity has received wide attention in clonal plant research over the last decade. Most studies have focussed on the effects of spatial variation in environmental conditions on the performance of ramets and genets, while the effects of temporal heterogeneity have only occasionally been studied. As a consequence, our current knowledge about functional responses of clonal plants to habitat patchiness is biased towards spatial aspects of environmental heterogeneity. Nevertheless, temporal changes in biotic and abiotic conditions do occur in most natural habitats, and they are very likely to affect plant growth and performance, and to create positive selection pressures on traits that can buffer plants against unfavorable consequences of this variability. Storage of resources is a widespread phenomenon in clonal plant species. Typical clonal structures such as stolons, rhizomes and hibernacles serve as storage organs. However, the ecologic significance of storage in clonal plant structures remains partly unclear. We suggest that the lack of understanding with respect to resource storage in clonal plants be related to our poor knowledge of ecologic implications of temporal habitat heterogeneity in natural environments. Resource storage can be understood as a safety measure against temporal changes in the growing conditions of plants. This paper summarizes existing information about the ecologic relevance of storage in clonal plants and it tries to develop a framework for further investigation of resource storage as a strategy to enhance the performance of clonal plants in temporally variable environments.
Guidance of neuronal growth cones in the grasshopper embryo. I. Recognition of a specific axonal pathway by the pCC neuron (1986)

The selective affinities that growth cones display for specific axonal surfaces give rise to stereotyped patterns of selective fasciculation. Previous studies on cell recognition by neuronal growth cones in the grasshopper embryo led to the proposal and initial experimental testing of the labeled-pathways hypothesis. Here we report on a further experimental analysis of this hypothesis, using the first 3 longitudinal axon fascicles, which initially contain only the axons of 7 identified neurons. We describe and experimentally test the selective affinity of the pCC growth cone for the MP1 and dMP2 axons in the MP1/dMP2 fascicle. The pCC growth cone appears to demonstrate an absolute, rather than hierarchical, preference for the MP1/dMP2 fascicle, as compared with other longitudinal axon fascicles, which supports the notion that the surfaces of the MP1 and dMP2 axons have some special distinguishing label that guides the pCC growth cone onto and along them.
Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats (2010)

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.
A New Genetic Vaccine Platform Based on an Adeno-Associated Virus Isolated from a Rhesus Macaque (2009)

We created a hybrid adeno-associated virus (AAV) from two related rhesus macaque isolates, called AAVrh32.33, and evaluated it as a vaccine carrier for human immunodeficiency virus type 1 (HIV-1) and type A influenza virus antigens. The goal was to overcome the limitations of vaccines based on other AAVs, which generate dysfunctional T-cell responses and are inhibited by antibodies found in human sera. Injection of a Gag-expressing AAVrh32.33 vector into mice resulted in a high-quality CD8(+) T-cell response. The resulting Gag-specific T cells express multiple cytokines at high levels, including interleukin-2, with many having memory phenotypes; a subsequent boost with an adenovirus vector yielded a brisk expansion of Gag-specific T cells. A priming dose of AAVrh32.33 led to high levels of Gag antibodies, which exceed levels found after injection of adenovirus vectors. Importantly, passive transfer of pooled human immunoglobulin into mice does not interfere with the efficacy of AAVrh32.33 expressing nucleoproteins from influenza virus, as measured by protection to a lethal dose of influenza virus, which is consistent with the very low seroprevalence to this virus in humans. Studies of macaques with vectors expressing gp140 from HIV-1 (i.e., with AAVrh32.33 as the prime and simian adenovirus type 24 as the boost) demonstrated results similar to those for mice with high-level and high-quality CD8(+) T-cell responses to gp140 and high-titered neutralizing antibodies to homologous HIV-1. The biology of this novel AAV hybrid suggests that it should be a preferred genetic vaccine carrier, capable of generating robust T- and B-cell responses.
Fixed‐Dose Vasopressin Compared with Titrated Dopamine and Norepinephrine as Initial Vasopressor Therapy for Septic Shock (2004)

Initial, fixed-dose vasopressin infusions increased MAP to 70 mm Hg or greater at 1 hour in intensive care patients with septic shock, similar to titrated norepinephrine or dopamine. Fixed-dose vasopressin appears appropriate as an alternative agent for hemodynamic support in patients with septic shock.
A Transistor Wire-Bonding System Utilizing Multiple Local Pattern Matching Techniques (1976)

A fully automatic transistor wire-bonding system utilizing image-processing techniques is described. The system is composed of a minicomputer, image processors, and a maximum of 50 wire-bonding machines. Each machine has a TV camera installed to pick up, through a microscope, the image of transistor chips fed into the machine. In this system, one image processor services several machines in a group and analyzes the image signals in a time-sharing mode to determine the chip position at each machine. From the detected coordinates, an XY servomechanism in each machine is activated to bond and stretch wires between the electrodes on the chip and the outer leads. The recognition of electrode positions is accomplished by the multiple local pattern matching method in which redundancy is used in achieving a high recognition rate. An analysis of the system and basic features of the position recognition algorithm are also described. This method opens the possibility of economical automation of processes possible only by the human eye to date.
p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes (2013)

Cellular senescence irreversibly arrests proliferation in response to potentially oncogenic stress. Senescent cells also secrete inflammatory cytokines such as IL-6, which promote age-associated inflammation and pathology. HMGB1 (high mobility group box 1) modulates gene expression in the nucleus, but certain immune cells secrete HMGB1 as an extracellular Alarmin to signal tissue damage. We show that nuclear HMGB1 relocalized to the extracellular milieu in senescent human and mouse cells in culture and in vivo. In contrast to cytokine secretion, HMGB1 redistribution required the p53 tumor suppressor, but not its activator ATM. Moreover, altered HMGB1 expression induced a p53-dependent senescent growth arrest. Senescent fibroblasts secreted oxidized HMGB1, which stimulated cytokine secretion through TLR-4 signaling. HMGB1 depletion, HMGB1 blocking antibody, or TLR-4 inhibition attenuated senescence-associated IL-6 secretion, and exogenous HMGB1 stimulated NF-κB activity and restored IL-6 secretion to HMGB1-depleted cells. Our findings identify senescence as a novel biological setting in which HMGB1 functions and link HMGB1 redistribution to p53 activity and senescence-associated inflammation.
Control of Membrane Sealing in Injured Mammalian Spinal Cord Axons (2000)

The process of sealing of damaged axons was examined in isolated strips of white matter from guinea pig spinal cord by recording the "compound membrane potential," using a sucrose-gap technique, and by examining uptake of horseradish peroxidase (HRP). Following axonal transection, exponential recovery of membrane potential occurred with a time constant of 20 +/- 5 min, at 37 degrees C, and extracellular calcium activity ([Ca(2+)](o)) of 2 mM. Most axons excluded HRP by 30 min following transection. The rate of sealing was reduced by lowering calcium and was effectively blocked at [Ca(2+)](o) </= 0.5 mM, under which condition most axons continued to take up HRP for more than 1 h. Sealing at higher [Ca(2+)](o) was blocked by calpain inhibitors (calpeptin and calpain inhibitor-1) indicating a requirement for type II (mM) calpain in the sealing process. Following compression injury, the amplitude of the maximal compound action potential conducted through the injury site was reduced. The extent of amplitude reduction was increased when the tract was superfused with calcium-free Krebs' solution (Ca(2+) replaced by Mg(2+)). These results suggest that the fall in [Ca(2+)](o) seen following injury in vivo is sufficient to prevent membrane sealing and may paradoxically contribute to axonal dieback, retrograde cell death, and "secondary" axonal disruption.
Characterization of infectivity of knob-modified adenoviral vectors in glioma (2008)

Malignant glioma continues to be a major target for gene therapy and virotherapy due to its aggressive growth and the current lack of effective treatment. However, these approaches have been hampered by inefficient infection of glioma cells by viral vectors,particularly vectors derived from serotype 5 adenoviruses (Ad5). This results from limited cell surface expression of the primary adenovirus receptor, coxsackie-adenovirus-receptor (CAR), on tumor cells. To circumvent this problem, Ad fiber pseudotyping,the genetic replacement of either the entire fiber or fiber knob domain with its structural counterpart from another human Ad serotype that recognizes a cellular receptor other than CAR, has been shown to enhance Ad infectivity in a variety of tumor types,including human glioma. Here, we have extended the paradigm of genetic pseudotyping to include fiber domains from non-human or"xenotype" Ads for infectivity enhancement of human glioma cell populations. In this study, we evaluated the gene transfer efficiency of a panel of Ad vectors which express one of five different "xenotype"fiber knob domains, including those derived from murine,ovine, porcine and canine species, in both human glioma cell lines as well as primary glioma tumor cells from patients. Adenovirus vectors displaying either canine Ad or porcine Ad fiber elements had the highest gene transfer to both glioma cell lines and primary tumor cells. The correlation between the viral infectivity of modified adenovirus vectors and expression of human CAR and CD46(an adenovirus type B receptor) on the surfaces of tumor cells was also analyzed. Taken together, human adenovirus vectors modified with "xenotype" fiber elements could be excellent candidates to target human glioma.
STUDIES ON ARTIFICIAL ANTIGENS (1963)

Dinitrophenyl conjugates of poly-L-lysine, varying in percentage conjugation and molecular weight have been found to induce skin reactivity and precipitating antibodies in guinea pigs. At best, 40 per cent of immunized animals developed delayed and immediate responses to DNP-polylysine, which is believed to reflect constitutional differences among the animals assayed. Only those animals capable of responding to DNP-polylysine, responded to an immunologically distinct poly-alpha-amino acid consisting of glutamyl and lysyl residues ("copolymer glu-lys"). The percentage of animals responding to the DNP-polylysine antigen decreased as the degree of DNP conjugation increased.
Relationship Between Sunlight Exposure and a Key Genetic Alteration in Basal Cell Carcinoma (1996)

The limited association between sunlight exposure and BCC incidence may reflect an etiologic contribution of additional environmental agents.
Clinical-Scale Derivation of Natural Killer Cells From Human Pluripotent Stem Cells for Cancer Therapy (2013)

Adoptive transfer of antitumor lymphocytes has gained intense interest in the field of cancer therapeutics over the past two decades. Human natural killer (NK) cells are a promising source of lymphocytes for anticancer immunotherapy. NK cells are part of the innate immune system and exhibit potent antitumor activity without need for human leukocyte antigen matching and without prior antigen exposure. Moreover, the derivation of NK cells from pluripotent stem cells could provide an unlimited source of lymphocytes for off-the-shelf therapy. To date, most studies on hematopoietic cell development from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have used incompletely defined conditions and been on a limited scale. Here, we have used a two-stage culture system to efficiently produce NK cells from hESCs and iPSCs in the absence of cell sorting and without need for xenogeneic stromal cells. This novel combination of embryoid body formation using defined conditions and membrane-bound interleukin 21-expressing artificial antigen-presenting cells allows production of mature and functional NK cells from several different hESC and iPSC lines. Although different hESC and iPSC lines had varying efficiencies in hematopoietic development, all cell lines tested could produce functional NK cells. These methods can be used to generate enough cytotoxic NK cells to treat a single patient from fewer than 250,000 input hESCs/iPSCs. Additionally, this strategy provides a genetically amenable platform to study normal NK cell development and education in vitro.
The Use of Specific Monoclonal Antibodies to Target Immunogenic Tumor Membrane Proteins in Patients with Recurrent Pancreatic and Colon Cancer (2011)

Tumor associated antigens from pooled allogeneic membrane proteins were isolated, partially purified and tested as a possible vaccine in patients with stage II and III colon cancer. The vaccine, when given in combination with an adjuvant following surgical resection, resulted in marked improvement in survival compared to control patients having only undergone surgical resection of their tumor. While it was possible to demonstrate that patients receiving vaccine turned on both humoral and cell mediated responses, it appears that survivors remaining free of disease at 5-7 yrs post op were able to mount a strong IgG1 response as the primary mechanism for tumor destruction. Antibodies from hybridomas made against the vaccines resulted in production of monoclonals with a high degree of ADCC. Those monoclonals targeting pancreatic cancer and in particular the MUC5ac mutated antigen representing tumor immunogen were studied in detail. Animal models indicated rapid tumor destruction when nude mice, injected with human pancreatic cancer were then immunized with NPC-1 monoclonal antibody targeting mutated MUC5ac. FDA studies including tissue cross reactivity, biodistribution, and cytokine release assays indicated safety and efficacy of the monoclonals we have developed. Submission of the IND allowed for initiation of the Phase I trial using mAb NPC-1 targeting pancreatic cancer when that antigen was found to be expressed.
Development of liposomal formulations: From concept to clinical investigations (2013)

Liposome is one of the most successful drug delivery systems applying nanotechnology to potentiate the therapeutic efficacy and reduce toxicities of conventional medicines. Since the first doxorubicin-loaded liposome reached the market, numerous researches have been carried out to develop new liposomal formulations over the past decade and have given birth to a series of commercial products. Therapeutic agents, most of which are anti-cancer drugs, are encapsulated in the aqueous core or lipid bilayers of liposomes to improve their delivery to the targeted tissue. There are several liposomal formulations, such as EndoTAG-1 (paclitaxel-loaded cationic liposomes), Lipoplatin (cisplatin-loaded long circulating liposomes) and Stimuvax (a cancer vaccine), showing promising therapeutic value in clinical studies. Besides, new designs including environmentally sensitive liposomes, liposomal drug combinations and liposomal vaccines are now tested in clinical trials.
Mixed Membership Stochastic Blockmodels. (2008)

Observations consisting of measurements on relationships for pairs of objects arise in many settings, such as protein interaction and gene regulatory networks, collections of author-recipient email, and social networks. Analyzing such data with probabilisic models can be delicate because the simple exchangeability assumptions underlying many boilerplate models no longer hold. In this paper, we describe a latent variable model of such data called the mixed membership stochastic blockmodel. This model extends blockmodels for relational data to ones which capture mixed membership latent relational structure, thus providing an object-specific low-dimensional representation. We develop a general variational inference algorithm for fast approximate posterior inference. We explore applications to social and protein interaction networks.
Antibody-Enhanced, Fc Gamma Receptor-Mediated Endocytosis of Clostridium difficile Toxin A (2009)

Toxin A (TcdA) and toxin B (TcdB) are major virulence factors of Clostridium difficile. These two toxins intoxicate cultured cells by similar mechanisms, and TcdB generally is more potent than TcdA in cultured cells. The exact reason for this difference is unclear. Here, we report that the cellular effects of TcdA can be substantially enhanced via an opsonizing antibody through Fc gamma receptor I (FcgammaRI)-mediated endocytosis. A TcdA-specific monoclonal antibody, A1H3, was found to significantly enhance the cytotoxicity of TcdA to macrophages and monocytes. The A1H3-dependent enhancement of glucosyltransferase activity, cytoskeleton disruption, and tumor necrosis factor alpha production induced by TcdA was further demonstrated using RAW 264.7 cells. Subsequent experiments indicated that the interaction of FcgammaRI with A1H3 underlays the antibody-dependent enhancement of the cellular effects of TcdA. While blocking FcgammaRII and FcgammaRIII with anti-CD16/32 antibodies did not affect the TcdA-mediated glucosylation of Rac1 in RAW 264.7 cells, presaturation of FcgammaRI with anti-CD64 antibodies in THP1 cells significantly reduced this activity. Incubation of a TcdA-A1H3 immune complex with recombinant mouse CD64 completely abrogated the A1H3-mediated enhancement of the glucosyltransferase activity of TcdA in RAW 264.7 cells. Moreover, expression of FcgammaRI in CHO cells strikingly enhanced the sensitivity of these cells to TcdA complexed with A1H3. We showed that the presence of A1H3 facilitated cell surface recruitment of TcdA, contributing to the antibody-dependent, FcgammaRI-mediated enhancement of TcdA activity. Finally, studies using chlorpromazine and endosomal acidification inhibitors revealed an important role of the endocytic pathway in the A1H3-dependent enhancement of TcdA activity.
CGAT: a comparative genome analysis tool for visualizing alignments in the analysis of complex evolutionary changes between closely related genomes (2006)

CGAT is a practical tool for analyzing complex genomic changes between closely related genomes using existing alignment programs and other sequence analysis tools combined with extensive manual inspection.
Motion-based segmentation and contour-based classification of video objects (2001)

The segmentation of objects in video sequences constitutes a prerequisite for numerous applications ranging from computer vision tasks to second-generation video coding.We propose an approach for segmenting video objects based on motion cues. To estimate motion we employ the 3D structure tensor, an operator that provides reliable results by integrating information from a number of consecutive video frames. We present a new hierarchical algorithm, embedding the structure tensor into a multiresolution framework to allow the estimation of large velocities.The motion estimates are included as an external force into a geodesic active contour model, thus stopping the evolving curve at the moving object's boundary. A level set-based implementation allows the simultaneous segmentation of several objects.As an application based on our object segmentation approach we provide a video object classification system. Curvature features of the object contour are matched by means of a curvature scale space technique to a database containing preprocessed views of prototypical objects.We provide encouraging experimental results calculated on synthetic and real-world video sequences to demonstrate the performance of our algorithms.