gebhart/patrepeval huggingface dataset:
The human Y4 small cytoplasmic RNA gene is controlled by upstream elements and resides on chromosome 7 with all other hY scRNA genes (1994)

Ro ribonucleoproteins (RNP) constitute a class of evolutionarily conserved small cytoplasmic (sc) RNPs whose functions are unknown. In human cells four distinctive scRNAs designated hY1, hY3, hY4 and hY5 are synthesized by RNA polymerase III (pol III) and accumulate as components of Ro scRNPs. The previously isolated hY1 and hY3 genes contain upstream sequences similar to the class III promoters for U6 and 7SK snRNAs. Additional mammalian Y scRNA genes have been refractory to cloning due to interference from numerous hY-homologous pseudogenes and studies of hY RNA genes have been sparse. Although homologs of hY1 and hY3 RNAs exist in rodent cells, the smaller Y4 and Y5 RNAs do not which has allowed us to localize the hY4 scRNA gene to human chromosome 7 by assaying for its transcript in rodent X human somatic cell hybrids (SCH). A chromosome 7-enriched yeast artificial chromosome (YAC) library was then screened and the authentic hY4 sequence was isolated by strepavidin--biotin-mediated hybrid-selection followed by poly(dA)-tailing and hemispecific PCR. The region upstream of the hY4 sequence contains a TATAAAA motif centered at -26, a candidate proximal sequence element at -63, and three octamer-like sequences located between -260 and -200. hY4 RNA is readily detectable on Northern blots after transient transfection of the hY4 gene into mouse cells but not after transfection of a construct in which the 5' flanking region was deleted. SCHs and chromosome 7-enriched YACs were used to demonstrate that all four hY RNA genes reside on human chromosome 7.
Suspended Graphene Sensors with Improved Signal and Reduced Noise (2010)

We report enhanced performance of suspended graphene field effect transistors (Gra-FETs) as sensors in aqueous solutions. Etching of the silicon oxide (SiO(2)) substrate underneath graphene was carried out in situ during electrical measurements of devices, which enabled systematic comparison of transport properties for same devices before and after suspension. Significantly, the transconductance of Gra-FETs in the linear operating modes increases 1.5 and 2 times when the power of low-frequency noise concomitantly decreases 12 and 6 times for hole and electron carriers, respectively, after suspension of graphene in solution from the SiO(2) substrate. Suspended graphene devices were further demonstrated as direct and real-time pH sensors, and complementary pH sensing with the same nanodevice working as either a p-type or n-type transistor was experimentally realized by offsetting the electrolyte gate potential in solution. Our results highlight the importance to quantify fundamental parameters that define resolution of graphene-based bioelectronics and demonstrate that suspended nanodevices represent attractive platforms for chemical and biological sensors.
Mechanism of shape change in chilled human platelets (1995)

The so-called cold activation of platelets that precludes refrigeration of platelets for storage has long been recognized, but its mechanism has remained a mystery. Cooling of discoid resting platelets to temperatures below 15 degrees C causes shape distortions, and the chilled cells rewarmed to above 25 degrees C are spheres rather than discs. As platelet shape change responsive to receptor activation at normal temperatures requires the remodeling of an actin scaffolding (Hartwig JH, 1992, J Cell Biol 118:1421-1442), we examined the role of actin in the morphologic changes induced by cooling. The addition of actin monomers onto the fast-exchanging (barbed) ends of actin filaments accompanies the initial physiologic platelet shape changes, and a key control point in this growth is the removal of proteins (caps) from the filament ends. This uncapping of actin filament ends is mediated by polyphosphoinositide aggregates in vitro, suggesting that cold-induced phase changes in membrane lipids might uncap actin filaments and thereby account for actin assembly-mediated shape alterations during cooling. Consistent with this hypothesis, reversible inhibition of actin assembly with cytochalasin B prevented the distortions in shape, although cooled platelets had increased actin nucleation sites and became spherical. Another step in normal platelet shape changes requires the severing of actin filaments that maintain the resting platelet. The proteins that sever initially bind to the broken filament ends, and uncapping of these fragmented filaments provides numerous nucleation sites for growth of actin filaments to fill in spreading filopodia and lamellae. Actin filament fragmentation requires a rise in intracellular calcium, and we showed that chilling platelets from 37 degrees C to 4 degrees C increases free cytosolic calcium levels from 80 nmol/L to approximately 200 nmol/L in minutes, thus providing an explanation for the spherical shape of cooled, rewarmed platelets. Blocking the calcium transient with nanomolar concentrations of the permeant calcium chelators Quin-2 and Fura-2 prevented the increase in nucleation sites and the sphering, but not the other shape changes of chilled and rewarmed platelets. However, a combination of micromolar cytochalasin B and millimolar intracellular calcium chelators preserved the discoid shapes of chilled and rewarmed platelets. After removal of cytochalasin B and addition of sufficient extracellular calcium, these platelets responded with normal morphologic alterations to glass and thrombin activation.
Progressive Renal Disease Established by Renin-Coding Adeno-Associated Virus–Driven Hypertension in Diverse Diabetic Models (2017)

Progress in research and developing therapeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting progressive kidney disease. Chronic hypertension, a driving factor of disease progression in human patients, is lacking in most available models of diabetes. We hypothesized that superimposition of hypertension on diabetic mouse models would accelerate DKD. To test this possibility, we induced persistent hypertension in three mouse models of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus delivery of renin (ReninAAV). Compared with LacZAAV-treated counterparts, ReninAAV-treated type 1 diabetic Akita/129 mice exhibited a substantial increase in albumin-to-creatinine ratio (ACR) and serum creatinine level and more severe renal lesions. In type 2 models of diabetes (C57BKLS <i>db/db</i> and BTBR <i>ob/ob</i> mice), compared with LacZAAV, ReninAAV induced significant elevations in ACR and increased the incidence and severity of histopathologic findings, with increased serum creatinine detected only in the ReninAAV-treated <i>db/db</i> mice. The uninephrectomized ReninAAV <i>db/db</i> model was the most progressive model examined and further characterized. In this model, separate treatment of hyperglycemia with rosiglitazone or hypertension with lisinopril partially reduced ACR, consistent with independent contributions of these disorders to renal disease. Microarray analysis and comparison with human DKD showed common pathways affected in human disease and this model. These results identify novel models of progressive DKD that provide researchers with a facile and reliable method to study disease pathogenesis and support the development of therapeutics.
A critical analysis of current in vitro and in vivo angiogenesis assays (2009)

The study of angiogenesis has grown exponentially over the past 40 years with the recognition that angiogenesis is essential for numerous pathologies and, more recently, with the advent of successful drugs to inhibit angiogenesis in tumours. The main problem with angiogenesis research remains the choice of appropriate assays to evaluate the efficacy of potential new drugs and to identify potential targets within the angiogenic process. This selection is made more complex by the recognition that heterogeneity occurs, not only within the endothelial cells themselves, but also within the specific microenvironment to be studied. Thus, it is essential to choose the assay conditions and cell types that most closely resemble the angiogenic disease being studied. This is especially important when aiming to translate data from in vitro to in vivo and from preclinical to the clinic. Here we critically review and highlight recent advances in the principle assays in common use including those for endothelial cell proliferation, migration, differentiation and co-culture with fibroblasts and mural cells in vitro, vessel outgrowth from organ cultures and in vivo assays such as chick chorioallantoic membrane (CAM), zebrafish, sponge implantation, corneal, dorsal air sac, chamber and tumour angiogenesis models. Finally, we briefly discuss the direction likely to be taken in future studies, which include the use of increasingly sophisticated imaging analysis systems for data acquisition.
Evidence for an increase in transcription of specific mRNAs during differentiation of 3T3-L1 preadipocytes. (1985)

Differentiation of 3T3-L1 preadipocytes in culture is accompanied by alterations in the abundance of several mRNAs and by the appearance of many new adipocyte-specific mRNAs. To investigate the processes responsible for these alterations, the kinetics of accumulation of several specific mRNAs were compared with their respective rates of nuclear runoff transcription. The mRNAs for fructose-1,6-bisphosphate aldolase and an unidentified 4800-base mRNA increase in abundance only moderately (2-4-fold) during differentiation. Runoff transcription by nuclei isolated from 3T3-L1 cells during the course of differentiation revealed very little or no change in the rates of transcription of these mRNAs. Similar results were obtained for the beta, alpha-actin and beta-tubulin mRNAs where no difference in nuclear runoff transcription rates were observed even though a 2-fold decrease in the steady-state levels of these mRNAs accompanies differentiation. In contrast, the steady-state levels of mRNAs for 3T3-L1 P2 protein, an adipocyte homologue of myelin P2 protein, and an unidentified 5000-base mRNA increased dramatically (greater than 20-fold) during adipose conversion. These large increases in abundance were correlated with marked rises (greater than 10-fold) in nuclear runoff transcription rates for these mRNAs during differentiation of 3T3-L1 preadipocytes. No change in runoff transcription activity for these mRNAs was detected by nuclei from control nondifferentiating 3T3-C2 cells. These results strongly suggest that an increased rate of specific transcription is primarily responsible for the accumulation of these mRNAs during preadipocyte differentiation.
Token and Notational Money in Electronic Commerce (1995)

What properties of money are important for electronic commerce? We argue that both transactional and privacy properties distinguish electronic commerce systems. We provide a quick overview of the history of money. We then consider privacy provided by different forms of money, and socially desirable disclosure of information as specified by legal reporting requirements. We classify electronic and traditional commerce systems into two categories:. token systems, which exchange markers representing value . notational systems, where value is stored as notations in a ledger or computer. We analyze different forms of traditional money based on the degree to which they protect the privacy and preserve transactional ACID (atomicity, consistency, isolation, durability) properties. Finally we apply our evaluation criteria to two proposed electronic commerce systems: Digicash, (Chaum, 1985; Chaum, 1992) a token-based system; and NetBill, (Sirbu, 1995) a notational system. 1 Token and Notationa...
Differential effects of cytokines on proliferative response of human CD4+ T lymphocyte subsets stimulated via T cell receptor-CD3 complex. (1990)

We report that the subsets of CD4+ T cells characterized by differential expression of CD45RA (2H4) Ag showed significant differences in proliferative response to immobilized anti-CD3 antibody (Ab) and cytokines: IL-1, IL-2, IL-4, and IL-6. Most strikingly, CD4+/45RA+ but not CD4+/45RA- T cells responded to anti-CD3 Ab and IL-4. Similar difference in response to IL-4 occurred when the subsets were stimulated by two "alternative" T cell activation pathways via CD2 and GD3 Ag. The response of CD4+/45RA+ cells to anti-CD3 Ab and IL-4 was enhanced by the two monokines: IL-1 and IL-6. Further differences between the subsets included the preferential response of the CD4+/45RA+ cells to enhancing effect of IL-6 on proliferation mediated by the anti-CD3 Ab and IL-2. In contrast to IL-6, IL-1 was unable to increase this proliferation significantly. In turn, the CD4+/45RA- cells responded preferentially to a weak stimulation mediated by anti-CD3 Ab either alone, or together with IL-1 and IL-6. Existence of these significant differences in the response of CD4+ T cell subsets costimulatory effects of the cytokines, suggests that the in vivo events resulting in an accumulation of the cytokines in particular combinations may lead to selective activation of one of the CD4+ T cell subsets during the immune response.
Ventricular pacing from the coronary sinus of a patient with a Fontan circulation. (1993)

Permanent pacing of the left ventricle was achieved by transvenous implantation of a steroid-eluting electrode into the coronary sinus in a patient who had undergone a Fontan operation. This approach to endocardial pacemaker implantation is potentially of considerable value in patients who do not have transvenous access to the right ventricle.
SLE: Mechanisms of Vascular Injury (1998)

The chronic elevation of complement split products seen in many patients with systemic lupus erythematosus should be regarded as equivalent to silent hypertension, or hyperglycemia in a patient with incipient diabetes mellitus. Although the consequences may not be immediately evident, such patients should be monitored and perhaps even treated.
Alternative, Non-secretase Processing of Alzheimer's β-Amyloid Precursor Protein during Apoptosis by Caspase-6 and -8 (1999)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Although the pathogenesis of AD is unknown, it is widely accepted that AD is caused by extracellular accumulation of a neurotoxic peptide, known as Abeta. Mutations in the beta-amyloid precursor protein (APP), from which Abeta arises by proteolysis, are associated with some forms of familial AD (FAD) and result in increased Abeta production. Two other FAD genes, presenilin-1 and -2, have also been shown to regulate Abeta production; however, studies examining the biological role of these FAD genes suggest an alternative theory for the pathogenesis of AD. In fact, all three genes have been shown to regulate programmed cell death, hinting at the possibility that dysregulation of apoptosis plays a primary role in causing neuronal loss in AD. In an attempt to reconcile these two hypotheses, we investigated APP processing during apoptosis and found that APP is processed by the cell death proteases caspase-6 and -8. APP is cleaved by caspases in the intracellular portion of the protein, in a site distinct from those processed by secretases. Moreover, it represents a general effect of apoptosis, because it occurs during cell death induced by several stimuli both in T cells and in neuronal cells.
Defective TNF-α-Induced Apoptosis in STAT1-Null Cells Due to Low Constitutive Levels of Caspases (1997)

Signal transducers and activators of transcription (STATs) enhance transcription of specific genes in response to cytokines and growth factors. STAT1 is also required for efficient constitutive expression of the caspases Ice, Cpp32, and Ich-1 in human fibroblasts. As a consequence, STAT1-null cells are resistant to apoptosis by tumor necrosis factor alpha (TNF-alpha). Reintroduction of STAT1alpha restored both TNF-alpha-induced apoptosis and the expression of Ice, Cpp32, and Ich-1. Variant STAT1 proteins carrying point mutations that inactivate domains required for STAT dimer formation nevertheless restored protease expression and sensitivity to apoptosis, indicating that the functions of STAT1 required for these activities are different from those that mediate induced gene expression.
The Majority of MicroRNAs Detectable in Serum and Saliva Is Concentrated in Exosomes (2012)

There is an increasing interest in using microRNAs (miRNA) as biomarkers in autoimmune diseases. They are easily accessible in many body fluids but it is controversial if they are circulating freely or are encapsulated in microvesicles, particularly exosomes. We investigated if the majority of miRNas in serum and saliva are free-circulating or concentrated in exosomes. Exosomes were isolated by ultracentrifugation from fresh and frozen human serum and saliva. The amount of selected miRNAs extracted from the exosomal pellet and the exosome-depleted serum and saliva was compared by quantitative RT-PCR. Some miRNAs tested are ubiquitously expressed, others were previously reported as biomarkers. We included miRNAs previously reported to be free circulating and some thought to be exosome specific. The purity of exosome fraction was confirmed by electronmicroscopy and western blot. The concentration of miRNAs was consistently higher in the exosome pellet compared to the exosome-depleted supernatant. We obtained the same results using an equal volume or equal amount of total RNA as input of the RT-qPCR. The concentration of miRNA in whole, unfractionated serum, was between the exosomal pellet and the exosome-depleted supernatant. Selected miRNAs, which were detectable in exosomes, were undetectable in whole serum and the exosome-depleted supernantant. Exosome isolation improves the sensitivity of miRNA amplification from human biologic fluids. Exosomal miRNA should be the starting point for early biomarker studies to reduce the probability of false negative results involving low abundance miRNAs that may be missed by using unfractionated serum or saliva.
Activins, Myostatin and Related TGF-β Family Members as Novel Therapeutic Targets for Endocrine, Metabolic and Immune Disorders (2004)

Activins and inhibins were first identified by virtue of their ability to regulate follicle-stimulating hormone (FSH) secretion from the anterior pituitary. Activins are also powerful regulators of gonadal functions. However, the physiological functions of activins are not restricted to reproductive tissues. Activins are involved in apoptosis of hepatocytes and B cells, fibrosis, inflammation and neurogenesis. Activins are regarded as novel drug targets since blocking activins would provide benefits by preventing apoptosis, fibrosis, inflammation and growth of several cancers. Activins are members of the transforming growth factor-beta (TGF-beta) family, which has numerous peptide growth and differentiation factors including activins, bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and TGF-betas. Among them, GDF8 is also known as myostatin and is structurally related to activins. Myostatin is specifically expressed in the skeletal muscle lineage and is a candidate for muscle chalone negatively regulating the growth of myoblasts. Myostatin is regarded as a good drug target since therapeutics that modulate skeletal muscle growth would be useful for disease conditions such as muscular dystrophy, sarcopenia, cachexia and even diabetes. Recent studies have revealed that activins and myostatin signal through activin type II receptors (ActRIIA and ActRIIB) and their activities are regulated by extracellular binding proteins, follistatins and follistatin-related gene (FLRG). Furthermore, signaling of activins, myostatin and related ligands is also controlled by intracellular receptor-interacting proteins by novel mechanisms. In this review, I would like to show the current progress in the field emphasizing the importance of activins and myostatin as novel drug targets for immune, endocrine and metabolic disorders.
Potential of Equine Herpesvirus 1 as a Vector for Immunization (2005)

Key problems using viral vectors for vaccination and gene therapy are antivector immunity, low transduction efficiencies, acute toxicity, and limited capacity to package foreign genetic information. It could be demonstrated that animal and human cells were efficiently transduced with equine herpesvirus 1 (EHV-1) reconstituted from viral DNA maintained and manipulated in Escherichia coli. Between 13 and 23% of primary human CD3+, CD4+, CD8+, CD11b+, and CD19+ cells and more than 70% of CD4+ MT4 cells or various human tumor cell lines (MeWo, Huh7, HeLa, 293T, or H1299) could be transduced with one infectious unit of EHV-1 per cell. After intranasal instillation of EHV-1 into mice, efficient transgene expression in lungs was detectable. Successful immunization using EHV-1 was shown after delivery of the human immunodeficiency virus type 1 Pr55gag precursor by the induction of a Gag-specific CD8+ immune response in mice. Because EHV-1 was not neutralized by human sera containing high titers of antibodies directed against human herpesviruses 1 to 5, it is concluded that this animal herpesvirus has enormous potential as a vaccine vector, because it is able to efficiently transduce a variety of animal and human cells, has high DNA packaging capacity, and can conveniently be maintained and manipulated in prokaryotic cells.
Origin of replication of colicin E1 plasmid DNA. (1977)

Cleavage maps of colicin E1 plasmid DNA and its smaller derivative, pNT1 DNA, were constructed by using restriction endonucleases. The nucleotide sequence of a region that contains the orgin of replication was determined. The site of the nucleotide from which DNA replication is initiated was determined with 6S L-fragments, the DNA fragment first made on colicin E1 plasmid DNA. The fragments were labeled with [gamma-32P]ATP and polynucleotide 5'-hydroxyl-kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) at the 5'-OH groups which were uncovered by alkali treatment. The site is one of three consecutive nucleotides, dA, dA, and dC, located at a unique position. One or a few rA residues were found to be attached to some of the DNA molecules. The transition from the primer RNA to DNA occurs in a region consisting of a segment of five A residues. Both sides of this segment are rich in G and C.
Crystal structure of anhydrous tripotassium citrate from laboratory X-ray powder diffraction data and DFT comparison (2016)

The crystal structure of anhydrous tripotassium citrate, [K3(C6H5O7)] n , has been solved and refined using laboratory X-ray powder diffraction data, and optimized using density functional techniques. The three unique potassium cations are 6-, 8-, and 6-coordinate (all irregular). The [KO n ] coordination polyhedra share edges and corners to form a three-dimensional framework, with channels running parallel to the c axis. The only hydrogen bond is an intra-molecular one involving the hy-droxy group and the central carboxyl-ate group, with graph-set motif S(5).
National Surveillance For Respiratory Syncytial Virus, United States, 1985-1990 (1994)

Respiratory syncytial virus (RSV) causes pneumonia and bronchiolitis in infants and young children and serious disease in the elderly and persons with compromised immune systems. To determine the temporal and geographic patterns of RSV outbreaks in the United States, monthly reports from 74 laboratories were analyzed for July 1985 through June 1990. RSV outbreaks were identified in 197 (93%) of the 211 laboratory years analyzed, with widespread activity beginning each fall, peaking in winter, and returning to baseline in April or May. Each year, the timing of outbreaks did not differ significantly between most regions; the few differences were small, and no region consistently had early or late outbreaks. These findings are consistent with RSV transmission within communities rather than between communities or regions. Health care personnel should consider the possibility of RSV infection in their treatment and prevention efforts from November through April each year in the United States.