gebhart/patrepeval huggingface dataset:
Tissue Inhibitor of Matrix Metalloproteinases-1 Impairs Arterial Neointima Formation After Vascular Injury in Mice (1999)

The hypothesis that tissue inhibitor of metalloproteinases-1 (TIMP-1) plays a role in neointima formation was tested with the use of a vascular injury model in wild-type (TIMP-1(+/+)) and TIMP-1-deficient (TIMP-1(-/-)) mice. The neointimal area at 1 to 3 weeks after electric injury of the femoral artery was significantly higher in TIMP-1(-/-) as compared with TIMP-1(+/+) mice (0.012+/-0. 0015 versus 0.0033+/-0.0008 mm(2) at 1 week, P<0.005). The medial areas were comparable, resulting in intima/media ratios that were significantly larger in TIMP-1(-/-) as compared with TIMP-1(+/+) arteries (1.2+/-0.22 versus 0.39+/-0.08 at 1 week, P<0.005). Nuclear cell counts in cross-sectional areas of the intima of the injured region were higher in TIMP-1(-/-) as compared with TIMP-1(+/+) arteries (138+/-15 versus 69+/-8 at 1 week, P<0.005). Immunocytochemical analysis revealed that alpha-actin-positive smooth muscle cells (SMCs) at 2 weeks after injury were more abundant in the intima of TIMP-1(-/-) arteries than in that of TIMP-1(+/+) arteries, whereas after 3 weeks the intimal cell population consisted mainly of SMCs in both genotypes. In in vitro scrape-wounding assays, SMCs of TIMP-1(-/-) mice migrated faster than those of TIMP-1(+/+) mice. Zymography of arterial extracts revealed a higher active matrix metalloproteinase (MMP)-2 level at 1 to 3 weeks after injury in TIMP-1(-/-) arteries, whereas active MMP-9 was only detected in TIMP-1(-/-) arteries at 1 week after injury. These data are compatible with a role of TIMP-1 in the impairment of SMC migration and neointima formation after vascular injury, as a result of inhibition of MMP activity.
Analysis of aberrant pre‐messenger RNA splicing resulting from mutations in ATP8B1 and efficient in vitro rescue by adapted U1 small nuclear RNA (2014)

We systematically characterized the molecular consequences of 14 ATP8B1 mutations at exon-intron boundaries associated with ATP8B1 deficiency and found that the majority resulted in total exon skipping. The amount of correctly spliced product inversely correlated with disease severity. Compensatory modified U1 snRNAs, complementary to mutated donor splice sites, were able to improve exon definition very efficiently and could be a novel therapeutic strategy in ATP8B1 deficiency as well as other genetic diseases.
Expression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis. (1992)

Macrophages are thought to play an important role in the pathologic changes associated with idiopathic pulmonary fibrosis (IPF). The mechanisms for increased monocyte/macrophage recruitment in IPF are unknown. Monocyte chemoattractant protein 1 (MCP-1) is the predominant monocyte chemoattractant secreted by a variety of different cell types in culture. We examined the expression of MCP-1 mRNA and its protein product in vivo in IPF and non-IPF lung specimens by in situ hybridization and immunocytochemistry. The cell types expressing MCP-1 in vivo were identified by immunostaining with specific antibodies. We demonstrated the expression of MCP-1 mRNA in pulmonary epithelial cells, in monocytes/macrophages, and in vascular endothelial and smooth muscle cells. Lung epithelial cells in patients with IPF strongly expressed MCP-1 mRNA and its protein product. In contrast, epithelial cells in non-IPF specimens did not express MCP-1 mRNA. Macrophages and vascular endothelial and smooth muscle cells were shown to express MCP-1 in both IPF and non-IPF lung specimens. These findings provide a basis for the understanding of the in vivo physiologic processes that mediate monocyte/macrophage recruitment and infiltration in the lung interstitium and the pathologic state contributing to an increased alveolar monocyte/macrophage population and inflammation in IPF.
Targeted, Needle‐Free Vaccinations in Skin using Multilayered, Densely‐Packed Dissolving Microprojection Arrays (2010)

Targeting of vaccines to abundant immune cell populations within our outer thin skin layers using miniaturized devices-much thinner than a needle and syringe, could improve the efficacy of vaccines (and other immunotherapies). To meet this goal, a densely packed dissolving microprojection array (dissolving Nanopatch) is designed, achieving functional miniaturization by 1) formulating small microneedles (two orders of magnitude smaller than a standard needle and syringe) and 2) multiple layering of the payload within microprojections with tight tolerances (of the order of a micrometer). The formulation method is suitable to many vaccines because it is without harsh or complex chemical processes, and it is performed at low temperatures and at a neutral pH. When the formulated dNPs are applied to skin, consistent and robust penetration is achieved, rapidly targeting the skin strata of interest (<5 min; significantly faster than larger dissolving microneedles that have been previously reported). Resultant diffusion is significantly enhanced within the dermis compared with the epidermis. Using two different antigens (ovalbumin and a commercial trivalent influenza vaccine [Fluvax2008]), the administration of these dissolving patches generate robust systemic immune responses in a mouse model. To the authors' knowledge, this is the first report of successful vaccination with any form of dissolving microneedles. The patches made by this method therefore have the potential for pain-free, needle-free, and effective vaccination in humans.
Host cell-derived complement control proteins CD55 and CD59 are incorporated into the virions of two unrelated enveloped viruses. Human T cell leukemia/lymphoma virus type I (HTLV-I) and human cytomegalovirus (HCMV) (1995)

The current study was undertaken to determine whether the human T cell leukemia/lymphoma oncovirus type I (HTLV-I) and the herpesvirus human cytomegalovirus (HCM) incorporate host cell-derived C regulatory proteins. Our experiments showed that both CD59 and CD55 were associated with the external membrane of HTLV-I derived from MT2 cells, since virus could be captured by mAbs to these proteins, and antisera to CD55 and CD59 induced C-mediated lysis of HTLV-I virions. Additionally, both CD55 and CD59 were detected by immunoblot analysis of purified HTLV-I. Purified HCMV produced in human foreskin fibroblasts (HFF) also contained both CD55 and CD59, as detected by immunoblot analysis. However, treatment with anti-CD55, but not anti-CD59, reduced the HCMV infectious titer in the presence of C. Additional studies determined whether HTLV-I-associated CD55 and CD59 participated in the resistance of the virus to C-mediated lysis. Treatment of virus with phosphatidylinositol-specific phospholipase C (PI-PLC), which removes glycosylphosphatidylinositol-anchored CD55 and CD59, increased the sensitivity of HTLV-I to C-mediated destruction in the presence of anti-HTLV-I Abs. Reconstitution of PI-PLC-treated virus with purified CD55 and CD59 restored resistance to C. These experiments show that HTLV-I and HCMV acquire C control proteins from host cells. Together with our previous experiments showing that both CD55 and CD59 are present on HIV-1, these studies demonstrate a mechanism by which a variety of enveloped viruses may acquire resistance to C-mediated destruction.
Use of a cloned multidrug resistance gene for coamplification and overproduction of major excreted protein, a transformation-regulated secreted acid protease. (1988)

Malignantly transformed mouse fibroblasts synthesize and secrete large amounts of major excreted protein (MEP), a 39,000-dalton precursor to an acid protease (cathepsin L). To evaluate the possible role of this protease in the transformed phenotype, we transfected cloned genes for mouse or human MEP into mouse NIH 3T3 cells with an expression vector for the dominant, selectable human multidrug resistance (MDR1) gene. The cotransfected MEP sequences were efficiently coamplified and transcribed during stepwise selection for multidrug resistance in colchicine. The transfected NIH 3T3 cell lines containing amplified MEP sequences synthesized as much MEP as did Kirsten sarcoma virus-transformed NIH 3T3 cells. The MEP synthesized by cells transfected with the cloned mouse and human MEP genes was also secreted. Elevated synthesis and secretion of MEP by NIH 3T3 cells did not change the nontransformed phenotype of these cells.
An EOQ Model for Items with Weibull Distributed Deterioration, Shortages and Power Demand Pattern (2002)

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PapD, a periplasmic transport protein in P-pilus biogenesis (1989)

The product of the papD gene of uropathogenic Escherichia coli is required for the biogenesis of digalactoside-binding P pili. Mutations within papD result in complete degradation of the major pilus subunit, PapA, and of the pilinlike proteins PapE and PapF and also cause partial breakdown of the PapG adhesin. The papD gene was sequenced, and the gene product was purified from the periplasm. The deduced amino acid sequence and the N-terminal sequence obtained from the purified protein revealed that PapD is a basic and hydrophilic peripheral protein. A periplasmic complex between PapD and PapE was purified from cells that overproduced and accumulated these proteins in the periplasm. Antibodies raised against this complex reacted with purified wild-type P pili but not with pili purified from a papE mutant. In contrast, anti-PapD serum did not react with purified pili or with the culture fluid of piliated cells. However, this serum was able to specifically precipitate the PapE protein from periplasmic extracts, confirming that PapD and PapE were associated as a complex. It is suggested that PapD functions in P-pilus biogenesis as a periplasmic transport protein. Probably PapD forms complexes with pilus subunits at the outer surface of the inner membrane and transports them in a stable configuration across the periplasmic space before delivering them to the site(s) of pilus polymerization.
A Model for Genetic and Epigenetic Regulatory Networks Identifies Rare Pathways for Transcription Factor Induced Pluripotency (2010)

With relatively low efficiency, differentiated cells can be reprogrammed to a pluripotent state by ectopic expression of a few transcription factors. An understanding of the mechanisms that underlie data emerging from such experiments can help design optimal strategies for creating pluripotent cells for patient-specific regenerative medicine. We have developed a computational model for the architecture of the epigenetic and genetic regulatory networks which describes transformations resulting from expression of reprogramming factors. Importantly, our studies identify the rare temporal pathways that result in induced pluripotent cells. Further experimental tests of predictions emerging from our model should lead to fundamental advances in our understanding of how cellular identity is maintained and transformed.
Video diabetes: a teaching tool for children with insulin-dependent diabetes (2005)

A computer game has been developed for children with insulin-dependent diabetes that combines the appeal of the video game and principles of diabetes control. The game is intended as a teaching tool to be used by the nurse-educator with the newly-diagnosed diabetic child, his family, or others responsible for the child's care. Throughout the course of a 24 hr. day, the player may enter choices for variable amounts of long acting and regular insulin, four types of meals ranging from pure glucose to a high protein-low carbohydrate meal, and four degree of exercise. At 5 minute intervals the blood sugar is plotted on the screen reflecting the changes the player has selected. A point score is displayed that is proportional to the proximity of the blood sugar to a normal range. At the end of the day, the nurse-educator can replay the day using a different video format that simultaneously plots the blood sugar, insulin and food absorption, urine spill and exercise values. In this format the interaction of each variable can be visualized and the net effect of these variables on the blood sugar is more meaningful. With knowledge of the first day, the player can try to improve his score on a subsequent day. Preliminary observations have shown that the game can hold a child's attention for hours. A study is currently underway to determine the impact of this interpretive teaching device on diabetic control.
Integration of Wet Oxidation and Nanofiltration for Treatment of Recalcitrant Organics in Wastewater (1997)

Wet oxidation and nanofiltration are employed in an integrated system for the treatment of bioresistant industrial wastewaters. The partial oxidation products formed during a brief period of pretreatment in a low pressure WO reactor are separated by nanofiltration, and larger molecules are recycled into the reactor where they undergo further oxidation. Experiments were carried out with polyethylene glycol as a model compound in aqueous solution, representing polymer manufacture wastewater. The results demonstrate that by using a combination of an oxidative and a separative step, a higher selectivity of the overall process toward partial oxidation can be achieved. The permeate leaving the filtration step is mainly composed of short chain organic acids which could be readily biodegraded in a subsequent biological treatment, or discharged if concentrations are low.
Cerebrovascular Pathology Contributes to the Heterogeneity of Alzheimer's Disease (1998)

Heterogeneous pathology in Alzheimer's Disease (AD) is due to variability in the nature and severity of lesions, overlap with other neurodegenerative diseases such as Parkinson's disease, or the co-existence of cerebrovascular disease. In the MGH-ADRC autopsy archives, remote cerebral infarcts (CVA) were reported in 30% of the otherwise uncomplicated AD cases. To determine the potential significance of cerebrovascular lesions in relation to AD, the relative densities (CERAD grading criteria) of Bielschowsky-stained AD lesions and Ab-amyloid immunoreactive plaques were compared among cases of AD+CVA (N=52), AD (N=48), aged controls (NC; N=9), and aged controls with AD lesions (ADC; N=8). The prevalence of the ApoE varepsilon 4 allele was also determined for each group. This study demonstrated: 1) higher densities of Bielschowsky-stained plaques in AD, AD+CVA, and ADC than in NC (P<0.0001); 2) more abundant neurofibrillary tangles in AD relative to all other groups (P<0.0005), and in AD+CVA and ADC relative to NC (P<0.05); and 3) increased densities of Ab-amyloid-immunoreactive plaques in AD relative to AD+CVA (P=0.0003). In AD+CVA, cerebral vascular lesions consisting of remote microscopic cortical and subcortical white matter infarcts, ischemic lesions, and leukoaraiosis were consistently distributed in structures typically damaged by AD neurodegeneration, as well as in the basal ganglia. The ApoE varepsilon 4 allele was more prevalent in the AD+CVA (70%) than in the AD (58%) group (P=0.05). Since the AD and AD+CVA groups had similar degrees of dementia, the results suggest that cerebral vascular lesions in regions typically destroyed by AD may contribute to the clinical manifestations of AD.
Granulocyte-Macrophage Colony Stimulating Factor: An Adjuvant for Cancer Vaccines (2004)

Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances immune responses by inducing the proliferation, maturation, and migration of dendritic cells, and the expansion and differentiation of B and T lymphocytes. There is significant data in pre-clinical animal models demonstrating the adjuvant effects of GM-CSF in a variety of cancer vaccine approaches, including cellular vaccines, viral vaccines, peptide and protein vaccines, and DNA vaccines. GM-CSF is an attractive vaccine adjuvant because of its immune modulation effects and low toxicity profile. The results in animal models have been confirmed in pilot clinical trials and several clinical trials are currently ongoing.
Anatomy of herpes simplex virus (HSV) DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 X HSV-2 recombinants (1978)

In an earlier paper (Morse et al., J. Virol 24:231--248, 1977) we reported on the provenance of the DNA sequences in 26 herpes simplex virus type 1 (HSV-1) X HSV-2 recombinants as determined from analyses of their DNAs with at least five restriction endonucleases. This report deals with the polypeptides specified by the recombinants and by their HSV-1 and HSV-2 parents. We have identified (i) the corresponding HSV-1 and HSV-2 polypeptides with molecular weights ranging from 20,000 to more than 200,000, (ii) the polypeptides that undergo rapid post-translational processing, and (iii) polypeptides that vary intratypically in apparent molecular weight. By comparing the segregation patterns of the polypeptides with those of the DNA sequence of the recombinants, we have mapped the templates specifying 26 polypeptides and several viral functions on the physical map of HSV DNA. The data show the following: (i) alpha polypeptides map at the termini of the L and S components of the HSV DNA. Although alpha ICP 27 maps entirely within the reiterated region of the L component, the template for alpha ICP 4 may lie only in part within the reiterated sequences of the S component. Of note is the finding that cells infected with a recombinant that contains both HSV-1 and HSV-2 DNA sequences in the S component produced alpha ICP 4 of both HSV-1 and HSV-2. (ii) Templates specifying beta and gamma polypeptides map in the L component and appear to be randomly distributed. (iii) Thymidine kinase and resistance to phosphonoacetic acid mapped in the L component. In addition, we have taken advantage of the rapid inhibition of host protein synthesis characteristic of HSV-2 infections and syncytial plaque morphology to also map the template(s) responsible for these functions in the L component. The implications of the template arrangement in HSV DNA are discussed.
Building Epithelial Tissues from Skin Stem Cells (2008)

The skin epidermis and its appendages provide a protective barrier that guards against loss of fluids, physical trauma, and invasion by harmful microbes. To perform these functions while confronting the harsh environs of the outside world, our body surface undergoes constant rejuvenation through homeostasis. In addition, it must be primed to repair wounds in response to injury. The adult skin maintains epidermal homeostasis, hair regeneration, and wound repair through the use of its stem cells. What are the properties of skin stem cells, when do they become established during embryogenesis, and how are they able to build tissues with such remarkably distinct architectures? How do stem cells maintain tissue homeostasis and repair wounds and how do they regulate the delicate balance between proliferation and differentiation? What is the relationship between skin cancer and mutations that perturbs the regulation of stem cells? In the past 5 years, the field of skin stem cells has bloomed as we and others have been able to purify and dissect the molecular properties of these tiny reservoirs of goliath potential. We report here progress on these fronts, with emphasis on our laboratory's contributions to the fascinating world of skin stem cells.
Pseudo-Gabor wavelet for face recognition (2013)

An efficient face-recognition algorithm is proposed, which not only possesses the advantages of linear subspace analysis approaches—such as low computational complexity—but also has the advantage of a high recognition performance with the wavelet-based algorithms. Based on the linearity of Gabor-wavelet transformation and some basic assumptions on face images, we can extract pseudo-Gabor features from the face images without performing any complex Gabor-wavelet transformations. The computational complexity can therefore be reduced while a high recognition performance is still maintained by using the principal component analysis (PCA) method. The proposed algorithm is evaluated based on the Yale database, the Caltech database, the ORL database, the AR database, and the Facial Recognition Technology database, and is compared with several different face recognition methods such as PCA, Gabor wavelets plus PCA, kernel PCA, locality preserving projection, and dual-tree complex wavelet transformation plus PCA. Experiments show that consistent and promising results are obtained.
VIS-Tracker: a wearable vision-inertial self-tracker (2003)

We present a demonstrated and commercially viable self-tracker, using robust software that fuses data from inertial and vision sensors. Compared to infrastructure-based trackers, self-trackers have the advantage that objects can be tracked over an extremely wide area, without the prohibitive cost of an extensive network of sensors or emitters to track them. So far, most AR research has focused on the long-term goal of a purely vision-based tracker that can operate in arbitrary unprepared environments, even outdoors. We instead chose to start with artificial fiducials, in order to quickly develop the first self-tracker which is small enough to wear on a belt, low cost, easy to install and self-calibrate, and low enough latency to achieve AR registration. We also present a roadmap for how we plan to migrate from artificial fiducials to natural ones. By designing to the requirements of AR, our system can easily handle the less challenging applications of wearable VR systems and robot navigation.
Neopterin and Biopterin Levels in Patients with Atypical Forms of Phenylketonuria (1980)

The pattern of unconjugated pterins in liver tissue and in urine from patients with atypical forms of phenylketonuria with hyperphenylalaninemia (HPA) has been investigated with a high performance liquid chromatographic technique. Two patients with defects in the biosynthesis of biopterin have been shown to have higher than normal levels of neopterin and lower than normal levels of biopterin. In contrast, a patient with HPA due to a deficiency of dihydropteridine reductase has the reverse urinary pattern, i.e., high biopterin, low neopterin. These results indicate that the ratio of neopterin to biopterin in urine can be of value in discriminating between HPA due to a deficiency of phenylalanine hydroxylase (classic PKU), HPA due to dihydropteridine reductase deficiency, and HPA due to a block in the biosynthesis of biopterin.
Photosensitizer Drug Delivery via an Optical Fiber (2011)

An optical fiber has been developed with a maneuverable mini-probe tip that sparges O(2) gas and photodetaches pheophorbide (sensitizer) molecules. Singlet oxygen is produced at the probe tip surface which reacts with an alkene spacer group releasing sensitizer upon fragmentation of a dioxetane intermediate. Optimal sensitizer photorelease occurred when the probe tip was loaded with 60 nmol sensitizer, where crowding of the pheophorbide molecules and self-quenching were kept to a minimum. The fiber optic tip delivered pheophorbide molecules and singlet oxygen to discrete locations. The 60 nmol sensitizer was delivered into petrolatum; however, sensitizer release was less efficient in toluene-d(8) (3.6 nmol) where most had remained adsorbed on the probe tip, even after the covalent alkene spacer bond had been broken. The results open the door to a new area of fiber optic-guided sensitizer delivery for the potential photodynamic therapy of hypoxic structures requiring cytotoxic control.
A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity (2009)

The successful design and synthesis of a novel multifunctional platinum drug candidate with DNA binding, histone deacetylase inhibitory activity and enhanced selectivity for cancer cells are described.