gebhart/patrepeval huggingface dataset:
Stage I clinical trial of gene therapy for hemophilia B. (1993)

This paper describes the first human gene therapy trial for hemophilia B. Retroviruses were used to introduce human factor IX into autologous, primary human skin fibroblasts from the patients. Recombinant retroviral vector containing human FIX cDNA driven by viral LTR promoter (XL-IX) and double-copy retroviral vector driven by human cytomegalovirus enhancer-promoter (N2CMV-IX) were constructed. After the safety assessment, including soft-agar test, cell morphology observation, analysis of endotoxin, chromosome karyotype, allergic reaction test, nude mice test, routine pathological test, electromicroscopic analysis, and virus detection by PCR, etc., the engineered cells were pooled and embedded in collagen mixture, autologously injected into the patients respectively. The concentration of human FIX protein of Patient 1 increased from 71 ng/ml to 220 ng/ml, with a maximum level of 245 ng/ml. The expression of FIX has lasted for 6 months at the time of writing. The clotting activity also increased from 2.9% to 6.3%, his clinical symptoms have been alleviated obviously. The secretion rate of FIX for Patient 2 increased from 130 to 250 ng/ml, maintained at the level of 220 ng/ml for 5.5 months at the time of writing, but the clotting activity has not been increased steadily. There is no deleterious effect to be found in the two patients since the ex-vivo cells were implanted. The two patients are now under follow-up investigation. We suggested that retrovirus-mediated transfer of genes into skin fibroblasts, to be embedded in collagen and subcutaneously injected into patients, is a simple and effective approach for the gene therapy for hemophilia B.
Growth of ultrathin SiO2 on Si by surface irradiation with an O2+Ar electron cyclotron resonance microwave plasma at low temperatures (1999)

Ultrathin SiO2 films were grown by Si surface irradiation with an O2+Ar electron cyclotron resonance (ECR) microwave plasma at low temperatures. These films without hydrogen and silicon deposition were easily grown in a few minutes at low temperatures and at relatively low working pressures (1.0–3.9×10−1 Pa). The promoting growth process of an ultrathin oxidized layer (1–9 nm) was analyzed by in situ Fourier transform infrared reflective absorption spectroscopy. By using the sputter erosion technique, the dependence of x-ray photoelectron spectroscopy on the depth profiling of the films was obtained. The compositional deviations of the films from the stoichiometric SiO2 were also discussed in the interface region of Si/SiO2. This study indicated that an O2 ECR microwave plasma was efficient to form controlled ultrathin SiO2 dielectric films. The dependence of the film quality on the working pressure and gas flow rate ratios of the O2 to Ar was discussed.
Initial chemotherapy for clinically localized lymphomas of unfavorable histology (1983)

Forty-five patients with localized non-Hodgkin's lymphoma of unfavorable histologic type (41 patients had diffuse histiocytic, 2 had nodular mixed, and 2 had minimally nodular histiocytic lymphoma) were treated with initial chemotherapy (28 patients), including cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP), or with initial CHOP followed by involved field radiotherapy (17 patients). Patients were clinically staged and found to have stage I (7 patients), stage IE (8), stage II (12), and stage IIE (18). Despite the presence of potentially adverse prognostic factors, including age older than 65 yr (11 patients), bulky disease (17), gastrointestinal involvement (9), and “B” symptoms (4), 44 of 45 patients (98%) achieved a complete response. Forty-two patients (93%) are alive with a median follow-up time of 41 mo (range 3–128 mo). Thirty-eight patients (84%) remain continuously free of disease. Neither the pretreatment clinical features nor the type of treatment significantly influenced the outcome for patients treated with initial chemotherapy. Patients who failed treatment relapsed at distant sites or in initially involved sites whether or not they received radiotherapy. Initial treatment for localized lymphomas of unfavorable histology with chemotherapy regimens of proven curative potential in advanced disease is a successful treatment strategy and obviates the need for extensive staging. The role of involved field radiotherapy following initial chemotherapy needs to be defined.
An exact solution for a reflection coefficient in a medium having an exponential impedance profile (1993)

An exact analytical solution for the plane wave reflection coefficient in an isotropic, constant velocity medium exhibiting an exponential impedance space profile is derived. The analysis includes the effects of discontinuities at both boundaries of the impedance transformer. The derivation is based on an exact differential equation that describes the space evolution of the reflection coefficient along a nonuniform transmission line. Power transmission curves for various cases, including the exact quarterwave case, are presented.
A membrane quadrant probe for R&D applications (2002)

Membrane probes are known for their applications to production probing and their ability to integrate RF lines, matching networks and good power supply bypassing for known good die testing on-wafer. Nonetheless, they require die-specific design and are not reconfigurable. In this paper, we discuss a quadrant probe based on membrane technology which offers this alternative with lower loss than membrane probes and better DC bypassing capability than any other quadrant probe.
Diabetic Retinopathy (2006)

Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation remains the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches to understand the pathophysiology and improve the detection, prevention, and treatment of retinopathy. This perspective considers how the unique anatomy and physiology of the retina may predispose it to the metabolic stresses of diabetes. The roles of neural retinal alterations and impaired retinal insulin action in the pathogenesis of early retinopathy and the mechanisms of vision loss are emphasized. Potential means to overcome limitations of current animal models and diagnostic testing are also presented with the goal of accelerating therapies to manage retinopathy in the face of ongoing diabetes.
Nuclear Export and Retention Signals in the RS Domain of SR Proteins (2002)

Splicing factors of the SR protein family share a modular structure consisting of one or two RNA recognition motifs (RRMs) and a C-terminal RS domain rich in arginine and serine residues. The RS domain, which is extensively phosphorylated, promotes protein-protein interactions and directs subcellular localization and-in certain situations-nucleocytoplasmic shuttling of individual SR proteins. We analyzed mutant versions of human SF2/ASF in which the natural RS repeats were replaced by RD or RE repeats and compared the splicing and subcellular localization properties of these proteins to those of SF2/ASF lacking the entire RS domain or possessing a minimal RS domain consisting of 10 consecutive RS dipeptides (RS10). In vitro splicing of a pre-mRNA that requires an RS domain could take place when the mutant RD, RE, or RS10 domain replaced the natural domain. The RS10 version of SF2/ASF shuttled between the nucleus and the cytoplasm in the same manner as the wild-type protein, suggesting that a tract of consecutive RS dipeptides, in conjunction with the RRMs of SF2/ASF, is necessary and sufficient to direct nucleocytoplasmic shuttling. However, the SR protein SC35 has two long stretches of RS repeats, yet it is not a shuttling protein. We demonstrate the presence of a dominant nuclear retention signal in the RS domain of SC35.
The Kidney in Liver Disease (2009)

This chapter contains sections titled: Impaired Renal Function in Liver Disease Acute Kidney Injury in Liver Disease Hepatorenal Syndrome Viral Infections Non-Alcoholic Fatty Liver Disease References
Osteochondral Allografts With an Intramedullary Muscle Flap in Rabbits (1997)

A model for hemijoint reconstruction using partially demineralized and lyophilized osteochondral allografts combined with an intramedullary muscle flap is described. The proximal 2/3 of the humerus was resected in 10 rabbits. The remaining defect was reconstructed with either a control lyophilized osteochondral allograft or a lyophilized allograft with a muscle flap filling the marrow cavity. Graft healing was followed by serial radiographs and magnetic resonance imaging. The grafts were harvested at 5 weeks for histologic analysis. By 5 weeks, 4 of 5 control allografts had fractured. In contrast, only 1 allograft with an intramedullary muscle flap showed evidence of a cortical break. Magnetic resonance imaging of control allografts showed a persistent large dead space within the marrow cavity and callus formation only at the outer cortical surface. Magnetic resonance imaging of allografts with an intramedullary muscle flap showed muscle obliterating the marrow cavity and areas of callus formation at both the outer and inner cortical surfaces. Histologically, graft incorporation was occurring at the outer cortical surface of the control allografts. In contrast, graft incorporation was occurring at both the outer and inner cortical surfaces of the allografts with an intramedullary muscle flap. The articular surface of the control allografts was severely degenerated. In allografts with an intramedullary muscle flap, the articular surface was smoother. Joints reconstructed with allografts with an intramedullary muscle flap had a significantly better range of motion at 5 weeks compared with control allografts. These results suggest that an intramedullary muscle flap can improve the functional results of joints reconstructed with partially demineralized and lyophilized osteochondral allografts by providing both vascularity and an increased population of mesenchymal stem cells capable of responding to bone morphogenetic proteins that reside in the partially demineralized allograft.
The Molecular Basis of Pancreatic Fibrosis (2004)

These genes are likely important factors in epithelial-stromal signaling in pancreatic desmoplasia and may serve as diagnostic or therapeutic targets.
Dissection of Semliki Forest virus glycoprotein delivery from the trans-Golgi network to the cell surface in permeabilized BHK cells. (1988)

In this paper mechanically permeabilized cells have been used to dissect the transport of Semliki Forest virus glycoproteins from the trans-Golgi network to the plasma membrane. Transport from the Golgi complex was monitored by measuring the proteolytic cleavage of the Semliki Forest virus p62 glycoprotein into the E2 and E3 polypeptide chains. Cell surface appearance was measured by the exposure of the exoplasmic domain to antibodies directed against the viral glycoprotein. Both the cleavage of the p62 protein and the transport of the glycoprotein to the cell surface were reconstituted in permeabilized BHK cells when calcium and glucose were present in the medium. Detailed analysis showed that the cleavage of the p62 protein occurred before arrival to the plasma membrane.
Sensing Pathogens and Tuning Immune Responses (2001)

The immune system is capable of making qualitatively distinct responses against different microbial infections, and recent advances are starting to reveal how it manages this complex task. An integral component of the immune system is a network of cells known as dendritic cells (DCs), which sense different microbial stimuli and convey this information to lymphocytes. A better understanding of DC biology has allowed a model to be constructed in which the type of immune response to an infection is viewed as a function of several determinants, including the subpopulation of DCs, the nature of the microbe, microbe recognition receptors, and the cytokine microenvironment.
Comparative virulence of human isolates of coagulase-negative staphylococci tested in an infant mouse weight retardation model (1989)

Human infections caused by coagulase-negative staphylococci have steadily increased in numbers and severity. Causes may be the use of artificial prostheses, immunocompromising chemotherapy and radiation therapy, and sophisticated surgical techniques, to name a few. Although the infectivity of coagulase-negative staphylococci as a group has been well documented for humans, attempts to study the pathogenesis of infections caused by individual species of coagulase-negative staphylococci have been hampered by the lack of an animal model that is not refractory to infection by these organisms. In the study reported here, a 2-day-old-mouse weight retardation test was used to assay the virulence of 60 clinical and reference strains of coagulase-negative staphylococci. These strains represented eight species of coagulase-negative staphylococci. The most virulent strains were demonstrated to be of the species Staphylococcus haemolyticus, S. saprophyticus, and S. epidermidis. The data further suggest that production of slime is a marker of virulence in S. epidermidis and that intraspecies differences in virulence occur.
Maximum power tracking in parallel connected converters (1993)

A control scheme for parallel connected converter systems that will transfer the maximum available power from a nonideal voltage source is presented. Monitoring the rates of change in both the average input current and average input power from the source in each switching period, the proposed control method can dynamically regulate the DC-DC converter system to track the peak power of the source. The amplitude and frequency of the oscillation due to a limit-cycle around the system peak power point is analyzed. In addition, the central-limit current distribution control for the system is incorporated in this control scheme to improve the system efficiency and reliability by uniformly distributing the total peak power among the converters connected in parallel.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Isolation of tumor cell growth-inhibiting factors from a human rhabdomyosarcoma cell line. (1985)

Two types of growth-modulating factors were derived from the serum-free conditioned media of a human rhabdomyosarcoma cell line, A673. One type, Mr 18,000 to 22,000, competes for binding to epidermal growth factor receptors and enhances the growth of normal and tumor cells in soft agar. It has all of the biological properties ascribed to transforming growth factor type alpha (TGF alpha). A673 cells also produce factors which inhibit the growth of human tumor cells in soft agar and in monolayer cultures. These tumor cell growth-inhibiting factors (TIFs) are acid- and heat-stable peptides. The major TIF activities have molecular weights in the ranges of greater than 28,000, 18,000 to 22,000, 10,000 to 16,000, and 5,000 to 10,000 and do not possess the antiviral activity associated with interferon. Partially purified preparations of TIF-1 (Mr 10,000 to 16,000) inhibit the growth of all human tumor cell lines tested and stimulate the growth of normal human fibroblasts and epithelial cells in monolayer cultures. The growth of human lung carcinoma A549 cells in soft agar, which was enhanced by treatment with TGF alpha from A673-conditioned media, was inhibited by treatment with TIF-1 derived from the same media. The ratio of the two types of tumor cell-derived, growth-modulating factors (TIFs and TGF alpha), which are antagonistic in their biological effects, may determine the capacity of tumor cells for anchorage-independent growth.
Variability in the X-ray warm absorber in GX 339-4 (2004)

We have previously reported evidence for a Seyfert-like warm absorber in the stellar-mass Galactic black hole GX 339-4, based on a Chandra/HETGS spectrum obtained during a 75 ksec observation during its 2002-2003 outburst starting on 2003 March 17.8 [1]. The ionized absorption lines detected with this observation were strong, but showed little variability on the timescale of the observation. Variability is perhaps the most important property for ascribing X-ray absorption lines to an accreting source, rather than to absorption in the ISM (which is also a possibility for GX 339-4).
Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier (2007)

Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR(+/+) mice were mostly resistant to 2.5% DSS, VDR(-/-) mice developed severe diarrhea, rectal bleeding, and marked body weight loss, leading to death in 2 wk. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR(-/-) mice. Severe ulceration in VDR(-/-) mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared with VDR(+/+) mice. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR(-/-) mice after 3-day DSS treatment. Therefore, VDR(-/-) mice were much more susceptible to DSS-induced mucosal injury than VDR(+/+) mice. In cell cultures, 1,25-dihydroxy-vitamin D(3) [1,25(OH)(2)D(3)] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)(2)D(3) can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.
All in one: VLP‐MUC1 vaccine for prevention and treatment of epithelial tumors (2008)

A promising target for immunotherapy, both for prophylactic and therapeutic vaccines, is the tumor antigen MUC1. Normally, the MUC1 glycoprotein is expressed at low levels on epithelial cells. However, MUC1 is hypoglycosylated and overexpressed on most adenocarcinomas of breast, pancreas, colon, ovary and lung. The goal of this project is to test a safe, practical and potentially very effective MUC1 vaccine using bovine papillomavirus like particles (BPV VLP) as a MUC1 delivery vehicle. BPV contains 2 capsid proteins, L1 and L2. L1 protein is made up of 12 &amp;#946; strands, 6 loops and 5 &amp;#945; helices and can self‐assemble into VLP. To enable conjugation of MUC1 and VLP, substitutions were made in the loop regions of the L1 molecule. Successful VLP formation following loop substitutions was achievable only in the HI loop where eight amino acids were replaced with negatively charged glutamic acid residues followed by a cysteine. Further, the MUC1 peptide was preceded by seven positively charged arginine and one cysteine residue. These substitutions allow the formation of a polyionic and a covalent bond that strengthens the conjugation between VLP and MUC1. Our preliminary results show that VLP‐MUC1 can cause the maturation of DC and that these DC can process and present the MUC1 peptide to a MUC1 specific T cell hybridoma. The potential of this vaccine to elicit an immune response, as well as tumor rejection is currently being evaluated.
A Brief Historical Perspective on Dental Implants, Their Surface Coatings and Treatments (2014)

This review highlights a brief, chronological sequence of the history of dental implants. This historical perspective begins with ancient civilizations and spotlights predominant dentists and their contributions to implant development through time. The physical, chemical and biologic properties of various dental implant surfaces and coatings are discussed, and specific surface treatments include an overview of machined implants, etched implants, and sand-blasted implants. Dental implant coatings such as hydroxyapatite, fluoride, and statin usage are further reviewed.
Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer. (2003)

Human mucin 1 (MUC1) is an epithelial mucin glycoprotein that is overexpressed in 90% of all adenocarcinomas including breast, lung, pancreas, prostate, stomach, colon, and ovary. MUC1 is a target for immune intervention, because, in patients with solid adenocarcinomas, low-level cellular and humoral immune responses to MUC1 have been observed, which are not sufficiently strong to eradicate the growing tumor. The hypothesis for this study is that enhancing MUC1-specific immunity will result in antitumor immunity. To test this, the authors have developed a clinically relevant breast cancer model that demonstrates peripheral and central tolerance to MUC1 and develops spontaneous tumors of the mammary gland. In these mice, the authors tested a vaccine formulation comprised of liposomal-MUC1 lipopeptide and human recombinant interleukin-2. Results indicate that when compared with untreated mice, immunized mice develop T cells that express intracellular IFN-gamma, are reactive with MHC class I H-2Db/MUC1 tetramer, and are cytotoxic against MUC1-expressing tumor cells in vitro. The presence of MUC1-specific CTL did not translate into a clinical response as measured by time of tumor onset, tumor burden, and survival. The authors demonstrate that some of the immune-evasion mechanisms used by the tumor cells include downregulation of MHC-class I molecule, expression of TGF-beta2, and decrease in IFN-gamma -expressing effector T cells as tumors progress. Finally, utilizing an injectable breast cancer model, the authors show that targeting a single tumor antigen may not be an effective antitumor treatment, but that immunization with dendritic cells fed with whole tumor lysate is effective in breaking tolerance and protecting mice from subsequent tumor challenge. A physiologically relevant spontaneous breast cancer model has been developed to test improved immunotherapeutic approaches.
Proliferation inhibition and apoptosis induction of human hepato-carcinoma HepG-2 cells by Phaeoporus obliquus polysaccharides (2009)

The effects of Phaeoporus obliquus polysaccharides on apoptosis of hepato-carcinoma HepG-2 cells were investigated. The inhibition of cell growth was determined by mono-nuclear cell direct cytotoxicity assay (MTT); morphological changes were observed by transmission electron microscopy; apoptosis was assessed by DNA ladder and flow cytometry (FCM). The mRNA expression levels of Bcl-2 and Bax genes were detected by reverse transcription-polymerase chain reaction (RT-PCR). Phaeoporus obliquus polysaccharides inhibited the growth of HepG-2 cells in vitro in dose-and time-dependent manner. Microscopic observation showed that the cells presented some morphologic features of apoptosis. Agarose gel electrophoresis analysis showed DNA ladder;hypodiploid peak appeared on flow cytometry (FCM) histogram, and the apoptotic rate of HepG-2 cells was risen with the increase of dose. The Bax mRNA expression was remarkably up-regulated in HepG-2 cells exposed to Phaeoporus obliquus polysaccharides, but no apparent changes of Bcl-2 gene were observed. Phaeoporus obliquus polysaccharides inhibit proliferation of HepG-2 cells and induce apoptosis. This may associate with upregulating of the expression of Bax gene.