gebhart/patrepeval huggingface dataset:
Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo (1996)

As part of a large-scale mutagenesis screen of the zebrafish genome, we have identified 58 mutations that affect the formation and function of the cardiovascular system. The cardiovascular system is particularly amenable for screening in the transparent zebrafish embryo because the heart and blood vessels are prominent and their function easily examined. We have classified the mutations affecting the heart into those that affect primarily either morphogenesis or function. Nine mutations clearly disrupt the formation of the heart. cloche deletes the endocardium. In cloche mutants, the myocardial layer forms in the absence of the endocardium but is dysmorphic and exhibits a weak contractility. Two loci, miles apart and bonnie and clyde, play a critical role in the fusion of the bilateral tubular primordia. Three mutations lead to an abnormally large heart and one to the formation of a diminutive, dysmorphic heart. We have found no mutation that deletes the myocardial cells altogether, but one, pandora, appears to eliminate the ventricle selectively. Seven mutations interfere with vascular integrity, as indicated by hemorrhage at particular sites. In terms of cardiac function, one large group exhibits a weak beat. In this group, five loci affect both chambers and seven a specific chamber (the atrium or ventricle). For example, the weak atrium mutation exhibits an atrium that becomes silent but has a normally beating ventricle. Seven mutations affect the rhythm of the heart causing, for example, a slow rate, a fibrillating pattern or an apparent block to conduction. In several other mutants, regurgitation of blood flow from ventricle to atrium is the most prominent abnormality, due either to the absence of valves or to poor coordination between the chambers with regard to the timing of contraction. The mutations identified in this screen point to discrete and critical steps in the formation and function of the heart and vasculature.
Longitudinal study of urinary 8-hydroxy-2′-deoxyguanosine excretion in healthy adults (2001)

Numerous studies have investigated the urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for the assessment of oxidative DNA damage in humans. In this study, we performed six consecutive series of measurement of urinary levels of 8-OHdG in 68 healthy probands, in order to provide information on the intra- and inter-individual variability of 8-OHdG and to estimate the influence of smoking, age, sex, body weight and body mass index (BMI) on the excretion of 8-OHdG. The intra-individual coefficient of variation (CV) of urinary 8-OHdG/24 h ranged from 0.18 to 1.06 (mean CV = 0.48). Women excreted significantly lower amounts of 8-OHdG/24 h than men, but the difference lost its significance when the body weight or urinary creatinine were used as covariates. By multiple linear regression analysis significant correlations between the mean individual levels of 8-OHdG/24 h excretion and urinary creatinine (rp = 0.61), and cotinine (rp = 0.27) have been observed, whereas no statistically significant effect of age, body weight and BMI was found. The 8-OHdG/creatinine ratio was found to be significantly increased in 23 smokers (1.95 +/- 0.40 mumol/mol) opposed to 45 non-smoking probands (1.62 +/- 0.50 mumol/mol), which is in good agreement with previously published data. No effect of passive smoking on the excretion of 8-OHdG was found. From our data we conclude that the intra-individual variability of urinary 8-OHdG excretion has been underestimated so far, indicating that values of 8-OHdG measured by single spot monitoring are not representative for individual base levels.
Analysis of Allogenicity of Mesenchymal Stem Cells in Engraftment and Wound Healing in Mice (2009)

Studies have shown that allogeneic (allo-) bone marrow derived mesenchymal stem cells (BM-MSCs) may enhance tissue repair/regeneration. However, recent studies suggest that immune rejection may occur to allo-MSCs leading to reduced engraftment. In this study, we compared allo-BM-MSCs with syngeneic BM-MSCs or allo-fibroblasts in engraftment and effect in wound healing. Equal numbers of GFP-expressing allo-BM-MSCs, syngeneic BM-MSCs or allo-fibroblasts were implanted into excisional wounds in GFP-negative mice. Quantification of GFP-expressing cells in wounds at 7, 14 and 28 days indicated similar amounts of allogeneic or syngeneic BM-MSCs but significantly reduced amounts of allo-fibroblasts. With healing progression, decreasing amounts of allogeneic and syngeneic BM-MSCs were found in the wound; however, the reduction was more evident (2 fold) in allo-fibroblasts. Similar effects in enhancing wound closure were found in allogeneic and syngeneic BM-MSCs but not in allo-fibroblasts. Histological analysis showed that allo-fibroblasts were largely confined to the injection sites while allo-BM-MSCs had migrated into the entire wound. Quantification of inflammatory cells in wounds showed that allo-fibroblast- but not allo-BM-MSC-treated wounds had significantly increased CD45+ leukocytes, CD3+ lymphocytes and CD8+ T cells. Our study suggests that allogeneic BM-MSCs exhibit ignorable immunogenicity and are equally efficient as syngeneic BM-MSCs in engraftment and in enhancing wound healing.
Modulation of LIGHT-HVEM Costimulation Prolongs Cardiac Allograft Survival (2002)

LIGHT (TNFSF14), a tumor necrosis factor superfamily member expressed by activated T cells, binds to herpes virus entry mediator (HVEM) which is constitutively expressed by T cells and costimulates T cell activation in a CD28-independent manner. Given interest in regulating the effector functions of T cells in vivo, we examined the role of LIGHT-HVEM costimulation in a murine cardiac allograft rejection model. Normal hearts lacked LIGHT or HVEM mRNA expression, but allografts showed strong expression of both genes from day 3 after transplant, and in situ hybridization and immunohistology-localized LIGHT and HVEM to infiltrating leukocytes. To test the importance of LIGHT expression on allograft survival, we generated LIGHT-/- mice by homologous recombination. The mean survival of fully major histocompatibility complex-mismatched vascularized cardiac allografts in LIGHT-/- mice (10 days, P < 0.05) or cyclosporine A (CsA)-treated LIGHT+/+ mice (10 days, P < 0.05) was only slightly prolonged compared with LIGHT+/+ mice (7 days). However, mean allograft survival in CsA-treated LIGHT-/- allograft recipients (30 days) was considerably enhanced (P < 0.001) compared with the 10 days of mean survival in either untreated LIGHT-/- mice or CsA-treated LIGHT+/+ controls. Molecular analyzes showed that the beneficial effects of targeting of LIGHT in CsA-treated recipients were accompanied by decreased intragraft expression of interferon (IFN)-gamma, plus IFN-gamma-induced chemokine, inducible protein-10, and its receptor, CXCR3. Treatment of LIGHT+/+ allograft recipients with HVEM-Ig plus CsA also enhanced mean allograft survival (21 days) versus wild-type controls receiving HVEM-Ig (mean of 7 days) or CsA alone (P < 0.001). Our data suggest that T cell to T cell-mediated LIGHT/HVEM-dependent costimulation is a significant component of the host response leading to cardiac allograft rejection.
Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response (2009)

Here, we describe an N-ethyl-N-nitrosourea (ENU)-induced missense error in the membrane-bound transcription factor peptidase site 1 (S1P)-encoding gene (Mbtps1) that causes enhanced susceptibility to dextran sodium sulfate (DSS)-induced colitis. S1P cleaves and activates cAMP response element binding protein/ATF transcription factors, the sterol regulatory element-binding proteins (SREBPs), and other proteins of both endogenous and viral origin. Because S1P has a nonredundant function in the ATF6-dependent unfolded protein response (UPR), woodrat mice show diminished levels of major endoplasmic reticulum chaperones GRP78 (BiP) and GRP94 in the colon upon DSS administration. Experiments with bone marrow chimeric mice reveal a requirement for S1P in nonhematopoietic cells, without which a diminished UPR and colitis develop.
35-GHz-Doppler radar for law enforcement agencies in Europe (2003)

An experimental program was conducted to investigate the reflectivity of moving motor vehicles using a Ka-band CW Doppler radar, as well as the accuracy of speed measurements as a function of parameters such as antenna polarization, beam illumination, side distance, multipath, antenna height, signal-to-interference ratio, and aspect angle. The experimental setup used a stationary dual-channel 35-GHz CW Doppler radar with selectable transmit polarization, direction-of-motion-sensing capability, and a signal recording system. The results of the experiments provide basic data for the design of law-enforcement radars at Ka-band. The dominant scatterers and their location on the vehicle were determined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Erythropoietin synthesis by tumor cells in a case of meningioma associated with erythrocytosis (1993)

While secondary erythrocytosis is often associated with tumors arising from the kidney, other tumors have been described to originate in the liver, uterus, ovary, adrenal gland, and central nervous system, among which cerebellar hemangioblastomas are involved in most instances. Two cases of meningioma associated with erythrocytosis have already been reported. We observed a 59-year-old female patient who had developed a frontal meningioma associated with erythrocytosis. Before surgery, she had a significantly elevated total red blood cell volume with a normal plasma volume. Serum erythropoietin (Epo) dosage assessed by radioimmunoassay was within the normal range. The tumor was removed and the pathologic study found a meningotheliomatous meningioma. Total RNA from the tumor was hybridized to a monkey cDNA Epo probe. A strong 1.6- kb messenger RNA (mRNA) signal was observed, which is the expected size of human Epo mRNA. In situ hybridization with the 35S-labeled Epo probe was performed on frozen tumor tissue sections. A significant hybridization was observed in all the tumor cells, whereas the stroma was negative. Therefore, in this meningioma associated with erythrocytosis, Epo was produced by the tumor cells themselves.
Nonirradiated NOD,B6.SCID Il2rγ−/− KitW41/W41 (NBSGW) Mice Support Multilineage Engraftment of Human Hematopoietic Cells (2015)

In this study, we demonstrate a newly derived mouse model that supports engraftment of human hematopoietic stem cells (HSCs) in the absence of irradiation. We cross the NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) strain with the C57BL/6J-Kit(W-41J)/J (C57BL/6.Kit(W41)) strain and engraft, without irradiation, the resulting NBSGW strain with human cord blood CD34+ cells. At 12-weeks postengraftment in NBSGW mice, we observe human cell chimerism in marrow (97% ± 0.4%), peripheral blood (61% ± 2%), and spleen (94% ± 2%) at levels observed with irradiation in NSG mice. We also detected a significant number of glycophorin-A-positive expressing cells in the developing NBSGW marrow. Further, the observed levels of human hematopoietic chimerism mimic those reported for both irradiated NSG and NSG-transgenic strains. This mouse model permits HSC engraftment while avoiding the complicating hematopoietic, gastrointestinal, and neurological side effects associated with irradiation and allows investigators without access to radiation to pursue engraftment studies with human HSCs.
Efficient photon harvesting at high optical intensities in ultrathin organic double-heterostructure photovoltaic diodes (2000)

We demonstrate a method for efficient photon harvesting in organic thin films, thereby increasing the efficiency of organic photovoltaic cells. By incorporating an exciton-blocking layer (EBL) inserted between the photoactive organic layers and the metal cathode, we achieved an external power conversion efficiency of 2.4%±0.3% in vacuum-deposited ultrathin organic bilayer photovoltaic (PV) cells employed in a simple light trapping geometry. Ultrathin (∼100 Å) cells incorporating the transparent, conductive EBL have an internal quantum efficiency as high as 33%±4% over a spectral region matched to the solar spectrum. The very thin organic layers have a low series resistance, allowing for efficient power conversion in organic PV cells under intense (&amp;gt;15 suns) AM1.5 illumination. This device structure demonstrates that control of exciton diffusion in solid-state organic devices leads to a significant increase in the photon-to-carrier conversion efficiency.
Importance of CD23 for Collagen-Induced Arthritis: Delayed Onset and Reduced Severity in CD23-Deficient Mice (1999)

Increased expression of the low affinity receptor for IgE, FcepsilonRII/CD23 has been observed in rheumatoid arthritis. In view of this, we have investigated the expression and influence of CD23 in collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. CD23+ cells were analyzed in lymph nodes of DBA/1 mice immunized with bovine collagen type II (BCII) in CFA or with CFA only. The percentage of CD23+ lymph node cells was increased in both BCII/CFA- and CFA-immunized mice at 1, 3, and 7 wk after immunization compared with unimmunized mice, indicating a role for the adjuvant to trigger general inflammation and CD23 expression. To investigate the functional role of CD23 in CIA, CD23-deficient mice on the DBA/1 genetic background were studied. After immunization with BCII/CFA, these mice developed CIA with delayed onset and reduced severity compared with wild-type mice. These findings suggest that an increased number of CD23+ cells is part of an inflammatory response and that CD23 expression is of pathogenic importance in the arthritic process.
FACS-optimized mutants of the green fluorescent protein (GFP) (1996)

We have constructed a library in Escherichia coli of mutant gfp genes (encoding green fluorescent protein, GFP) expressed from a tightly regulated inducible promoter. We introduced random amino acid (aa) substitutions in the twenty aa flanking the chromophore Ser-Tyr-Gly sequence at aa 65-67. We then used fluorescence-activated cell sorting (FACS) to select variants of GFP that fluoresce between 20-and 35-fold more intensely than wild type (wt), when excited at 488 nm. Sequence analysis reveals three classes of aa substitutions in GFP. All three classes of mutant proteins have highly shifted excitation maxima. In addition, when produced in E. coli, the folding of the mutant proteins is more efficient than folding of wt GFP. These two properties contribute to a greatly increased (100-fold) fluorescence intensity, making the mutants useful for a number of applications.
Expression of DNA methyltransferases DNMT1,3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia (2001)

Aberrant hypermethylation of tumor suppressor genes plays an important role in the development of many tumors. Recently identified new DNA methyltransferase (DNMT) genes, DNMT3A and DNMT3B, code for de novo methyltransferases. To determine the roles of DNMT3A, DNMT3B, as well as DNMT1, in the development of leukemia, competitive polymerase chain reaction (PCR) assays were performed and the expression levels of DNMTs were measured in normal hematopoiesis, 33 cases of acute myelogenous leukemia (AML), and 17 cases of chronic myelogenous leukemia (CML). All genes were constitutively expressed, although at different levels, in T lymphocytes, monocytes, neutrophils, and normal bone marrow cells. Interestingly, DNMT3B was expressed at high levels in CD34(+) bone marrow cells but down-regulated in differentiated cells. In AML, 5.3-, 4.4-, and 11.7-fold mean increases were seen in the levels of DNMT1, 3A, and 3B, respectively, compared with the control bone marrow cells. Although CML cells in the chronic phase did not show significant changes, cells in the acute phase showed 3.2-, 4.5-, and 3.4-fold mean increases in the levels of DNMT1, 3A, and 3B, respectively. Using methylation-specific PCR, it was observed that the p15(INAK4B) gene, a cell cycle regulator, was methylated in 24 of 33 (72%) cases of AML. Furthermore, AML cells with methylated p15(INAK4B) tended to express higher levels of DNMT1 and 3B. In conclusion, DNMTs were substantially overexpressed in leukemia cells in a leukemia type- and stage-specific manner. Up-regulated DNMTs may contribute to the pathogenesis of leukemia by inducing aberrant regional hypermethylation. (Blood. 2001;97:1172-1179)
Translational Systems Biology of Inflammation (2008)

Inflammation is a complex, multi-scale biologic response to stress that is also required for repair and regeneration after injury. Despite the repository of detailed data about the cellular and molecular processes involved in inflammation, including some understanding of its pathophysiology, little progress has been made in treating the severe inflammatory syndrome of sepsis. To address the gap between basic science knowledge and therapy for sepsis, a community of biologists and physicians is using systems biology approaches in hopes of yielding basic insights into the biology of inflammation. "Systems biology" is a discipline that combines experimental discovery with mathematical modeling to aid in the understanding of the dynamic global organization and function of a biologic system (cell to organ to organism). We propose the term translational systems biology for the application of similar tools and engineering principles to biologic systems with the primary goal of optimizing clinical practice. We describe the efforts to use translational systems biology to develop an integrated framework to gain insight into the problem of acute inflammation. Progress in understanding inflammation using translational systems biology tools highlights the promise of this multidisciplinary field. Future advances in understanding complex medical problems are highly dependent on methodological advances and integration of the computational systems biology community with biologists and clinicians.
Microbial Biofilms in Urinary Tract Infections and Prostatitis: Etiology, Pathogenicity, and Combating strategies (2016)

Urinary tract infections (UTIs) are one of the most important causes of morbidity and health care spending affecting persons of all ages. Bacterial biofilms play an important role in UTIs, responsible for persistent infections leading to recurrences and relapses. UTIs associated with microbial biofilms developed on catheters account for a high percentage of all nosocomial infections and are the most common source of Gram-negative bacteremia in hospitalized patients. The purpose of this mini-review is to present the role of microbial biofilms in the etiology of female UTI and different male prostatitis syndromes, their consequences, as well as the challenges for therapy.
Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization (2003)

Application of ultraviolet (UV) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted within 10 s in an insoluble, flexible hydrogel. A low molecular weight acidic molecule like trypan blue and various high molecular weight molecules such as bovine serum albumin (BSA), heparin and protamine were all retained within the hydrogel, while a low molecular weight basic molecule like toluidine blue was rapidly released from the hydrogel. In the present work, we examined the retaining capability of the chitosan hydrogel for growth factors and controlled release of growth factors from the chitosan hydrogel in vitro and in vivo. Fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor(165) (VEGF(165)), heparin-binding epidermal growth factor (HB-EGF) in phosphate buffered saline (PBS) were mixed with Az-CH-LA aqueous solution to form growth factor-incorporated chitosan hydrogels. About 10-25% of the growth factor was released from a growth factor-incorporated chitosan hydrogel into PBS within the first day, after which no further substantial release took place. The growth factors interacted with Az-CH-LA molecules poly-ion complexation, and probably were unable to be released after the first day under the in vitro nondegradation conditions of the hydrogel. Although the FGF-1, FGF-2, and VEGF(165)-incorporated chitosan hydrogels on a culture plate significantly stimulated HUVEC growth, the stimulating activity of the growth factor-incorporated chitosan hydrogel was completely cancelled out by washing the hydrogel with PBS solution for 3 days or more. The stimulating activity on the HUVEC growth were however highly recovered by treating the washed growth factor-incorporated chitosan hydrogel during 7 days with chitinase and chitosanase to partly degrade the hydrogel, strongly suggesting that the growth factors within the hydrogel retained their biologically active forms. The chitosan hydrogel (100 microl) when implanted into the back of a mouse was biodegraded in about 10-14 days. When FGF-1- and FGF-2-incorporated chitosan hydrogels were subcutaneously implanted into the back of a mouse, significant neovascularization was induced near the implanted site of the FGF-1- and FGF-2-incorporated chitosan hydrogels. Furthermore, addition of heparin with either FGF-1 or FGF-2 into the hydrogel resulted in a significantly enhanced and prolonged vascularization effect. These results indicate that the controlled release of biologically active FGF-1 and FGF-2 with heparin is caused by biodegradation of the chitosan hydrogel, and subsequent induction of vascularization.
Type 1 Diabetes Manifested Solely by 2-h Oral Glucose Tolerance Test Criteria (2001)

The clinical presentation of type 1 diabetes usually involves symptoms such as polyuria and polydipsia. However, investigators in the Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) have detected a group of subjects with type 1 diabetes who have a different phenotype. These subjects are asymptomatic, have normal (<6.1 mmol/l) (group A) or impaired (6.1- <7.0 mmol/l) (group B) fasting glucose, but have 2-h glucose values >11.1 mmol/l on their oral glucose tolerance tests (OGTT). Of the 585 OGTTs performed on islet cell antibody (ICA)-positive relatives with insulin autoantibodies (IAA) or low first-phase insulin response (FPIR), normal glucose tolerance (NGT) was found in 427 subjects; impaired glucose tolerance (IGT) was found in 87 subjects, and diabetes was found by 2-h OGTT criteria alone in 61 subjects. Despite marked differences in 2-h glucose values (NGT 5.8 +/- 1.1 mmol/l, IGT 8.9 +/- 0.9 mmol/l, and group A 13.5 +/- 2.5 mmol/l), there were no significant differences in fasting glucose values among NGT (4.8 +/- 0.5 mmol/l), IGT (5.03 +/- 0.5 mmol/l), and group A (4.99 +/- 0.7 mmol/l) categories. Mean FPIR was higher in subjects with NGT compared with subjects with IGT and subjects diagnosed by 2-h OGTT criteria alone. However, the correlation between FPIR and 2-h glucose value was low (r2 = 0.114). Multivariate analysis demonstrated that additional independent variables provide smaller contributions to the 2-h glucose value. In conclusion, there are asymptomatic type 1 diabetic subjects whose diabetes was diagnosed by the 2-h criteria on OGTT alone. Despite the importance of beta-cell dysfunction in the pathogenesis of type I diabetes, factors other than impaired FPIR must also contribute to postprandial glucose tolerance in these subjects.
Mouse Hematopoietic Stem Cell Transplantation (2013)

Hematopoietic stem cells (HSCs) are capable of self-renewal and multi-lineage reconstitution of hematopoiesis in irradiated transplant recipient mice. As such, bone marrow transplantation (BMT) is a major assay commonly used to examine murine HSC activity. BMT traditionally involves injection of HSCs into lethally irradiated recipients via the tail vein, then subsequently analyzing donor engraftment. Here, we describe the methods for assaying HSC reconstitution in direct, competitive, and serial BMT.