gebhart/patrepeval huggingface dataset:
Nkx6.1 Is Essential for Maintaining the Functional State of Pancreatic Beta Cells (2013)

Recently, loss of beta-cell-specific traits has been proposed as an early cause of beta cell failure in diabetes. However, the molecular mechanisms that underlie the loss of beta cell features remain unclear. Here, we identify an Nkx6.1-controlled gene regulatory network as essential for maintaining the functional and molecular traits of mature beta cells. Conditional Nkx6.1 inactivation in adult mice caused rapid-onset diabetes and hypoinsulinemia. Genome-wide analysis of Nkx6.1-regulated genes and functional assays further revealed a critical role for Nkx6.1 in the control of insulin biosynthesis, insulin secretion, and beta cell proliferation. Over time, Nkx6.1-deficient beta cells acquired molecular characteristics of delta cells, revealing a molecular link between impaired beta cell functional properties and loss of cell identity. Given that Nkx6.1 levels are reduced in human type 2 diabetic beta cells, our study lends support to the concept that loss of beta cell features could contribute to the pathogenesis of diabetes.
Molecular mapping of the mouse db mutation. (1990)

Diabetes (db) is an autosomal recessive mutation located in the midportion of mouse chromosome 4 that results in profound obesity with hyperphagia, increased metabolic efficiency, and insulin resistance. To clone this gene and generate a molecular map of the region around this mutation, two genetic crosses were established: an intraspecific backcross between C57BL/6J db/db females and C57BL/6J db/db x DBA/2J +/+ F1 (B6D2 db/+ F1) male mice and an interspecific intercross between B6D2 db/+ F1 males and C57BL/6J db/db x Mus spretus F1 (B6spretus db/+ F1) females. The progeny of both crosses were characterized for genotype at the db locus to map a series of restriction fragment length polymorphisms relative to the db locus. Measurements of body weight, body length, and plasma concentrations of glucose and insulin in the animals allowed the assignment of genotype (db/db vs. db/+ or +/+). A total of 132 progeny of the intraspecific cross and 48 db/db progeny of the interspecific cross were typed for individual restriction fragment length polymorphisms to generate a gene order of: centromere-brown (Mt4)-P lambda Mm3(2)-Ifa (Inta)-Cjun-db-D4Rp1-Glut1-Mtv-13-Lck. Several of the genes that are linked to db [Cjun, glucose transporter (Glut1) and Lck] map to human chromosome 1p, suggesting that db may be part of a syntenic group between human 1p and the distal portion of mouse chromosome 4. In addition, phenotyping of the progeny of these crosses revealed a wide range in plasma concentrations of glucose and insulin among the obese progeny, with some animals developing overt diabetes and other remaining euglycemic. Distributions of age-controlled plasma [glucose] and [insulin] among the intraspecific-cross obese progeny were not bimodal, suggesting a role for polygenic differences between the progenitor strains (C57BL/6J and DBA/2J) in the development of overt diabetes.
Fabrication of nanoelectromechanical systems in single crystal silicon using silicon on insulator substrates and electron beam lithography (1997)

We have demonstrated a process for fabricating nanometer-scale electromechanical structures of diverse geometries in single crystal silicon, using silicon on insulator substrates. We pattern the substrate using high resolution electron beam lithography with 100 keV electrons followed by Al evaporation and liftoff. The Al is used as an etch mask in CF4 reactive ion etching to pattern the top silicon layer. We then undercut structures using a buffered oxide etch. The structures were made from substrates having a top silicon thickness of 200 or 50 nm, and a buried oxide thickness of 400 nm. With this process we have made a variety of movable structures. We describe the performance of an electrostatically driven Fabry–Perot interferometer that consists of a μm sized pad suspended by wires that are 100–200 nm wide. We have also made much smaller mechanical structures such as suspended silicon beams as narrow as 30 nm.
Stem cells--prospects in dentistry. (2010)

Stem cell biology, an emerging field of research, provides promising methods in vitro as well as in vivo in animal models which make speculation about a future application in human dentistry reasonable. The objective of this study was to review the literature of stem cell research concerning fields relevant for dentistry. In dentistry, different stem cells are discussed. Adult dental ectomesenchymal stem cells seem promising for future therapy. Human stem cells have been isolated from the dental pulp, exfoliated deciduous teeth, the periodontal ligament, the dental follicle and the dental papilla. Stem cell markers such as STRO-1 were used for the characterization and isolation of stem cells. Adult dental stem cells can differentiate into many dental components, such as dentin, periodontal ligament, cement and dental pulp tissue, but not into enamel.
STUDIES ON VI ANTIGEN (1954)

Journal Article STUDIES ON VI ANTIGEN: VI. IMMUNIZATION OF HUMAN BEINGS WITH PURIFIED VI ANTIGEN Get access MAURICE LANDY MAURICE LANDY Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 60, Issue 1, July 1954, Pages 52–62, https://doi.org/10.1093/oxfordjournals.aje.a119703 Published: 01 July 1954 Article history Received: 12 April 1954 Published: 01 July 1954
The Use of a Flagellar Export Signal for the Secretion of Recombinant Proteins in Salmonella (2011)

The flagellum-specific export system is a specialized type III export machinery, which exports external flagellar proteins through the central channel of the flagellar filament. A number of evidence indicates that short segments within the disordered N-terminal region of flagellar axial proteins are recognized by the flagellum-specific export apparatus. Recently, we have demonstrated that the 26-47 segment of Salmonella typhimurium flagellin is capable of mediating flagellar export. N-terminal flagellin segments containing the export signal combined with a hexahistidine tag can be attached to heterologous proteins (preferentially in the size range of 9-40 kDa) facilitating their secreted expression and easy purification from the medium. Certain over-expressed proteins that are easily degraded within the cells are found intact in the medium implying a potential application of this expression system for proteins of high proteolytic susceptibility.
Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains (2000)

This study concerns chimeric restriction enzymes that are hybrids between a zinc finger DNA-binding domain and the non-specific DNA-cleavage domain from the natural restriction enzyme FOK:I. Because of the flexibility of DNA recognition by zinc fingers, these enzymes are potential tools for cleaving DNA at arbitrarily selected sequences. Efficient double-strand cleavage by the chimeric nucleases requires two binding sites in close proximity. When cuts were mapped on the DNA strands, it was found that they occur in pairs separated by approximately 4 bp with a 5' overhang, as for native FOK:I. Furthermore, amino acid changes in the dimer interface of the cleavage domain abolished activity. These results reflect a requirement for dimerization of the cleavage domain. The dependence of cleavage efficiency on the distance between two inverted binding sites was determined and both upper and lower limits were defined. Two different zinc finger combinations binding to non-identical sites also supported specific cleavage. Molecular modeling was employed to gain insight into the precise location of the cut sites. These results define requirements for effective targets of chimeric nucleases and will guide the design of novel specificities for directed DNA cleavage in vitro and in vivo.
Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting (2018)

This strategy has the potential for preparing custom LNPs with endless varieties of structures and final <i>pKa</i> values, and would have poten tial applications in drug delivery and ionic-based tissue targeting.
Organic electroluminescent diodes (1987)

A novel electroluminescent device is constructed using organic materials as the emitting elements. The diode has a double-layer structure of organic thin films, prepared by vapor deposition. Efficient injection of holes and electrons is provided from an indium-tin-oxide anode and an alloyed Mg:Ag cathode. Electron-hole recombination and green electroluminescent emission are confined near the organic interface region. High external quantum efficiency (1% photon/electron), luminous efficiency (1.5 lm/W), and brightness (&amp;gt;1000 cd/m2) are achievable at a driving voltage below 10 V.
Endothelin Converting Enzyme Inhibitors (1997)

Endothelins (ETs) are a family of potent, peptidic vasoconstrictors and are implicated in the involvement of a variety of cardiovascular, renal, and central nervous system diseases. The final step of post-translational processing of these peptides is catalyzed by endothelin converting enzyme (ECE), a zinc metalloprotease. Inhibitors of this enzyme are expected to suppress the biosynthesis of ETs and provide an alternate approach to the ETA/ETB receptor antagonism. The biochemical characteristics of ECE are briefly reviewedin this article. The main focus is on the design and pharmacological properties of various classes of ECE inhibitors, including peptides, natural products, and low molecular weight molecules featuring a phosphorus-containirrg functionality, a sulfhydryl, a hydroxamic acid, or a carboxylic acid as the zinc-binding group. Compounds such as phosphoramidon, CGS 26303, and SCH 54470 have been shown to be efficacious in experimental models of hypertension, chronic heart failure, cerebral vasospasm following subarachnoid hemorrhage, and renal failure. Thus, ECE inhibitors may represent a new class of agents for the treatment of diseases where an overproduction of ETs plays a pathogenic role.
In Vitro Selection of RNA Molecules That Inhibit the Activity of Ricin A-chain (2000)

The cytotoxin ricin disables translation by depurinating a conserved site in eukaryotic rRNA. In vitro selection has been used to generate RNA ligands (aptamers) specific for the catalytic ricin A-chain (RTA). The anti-RTA aptamers bear no resemblance to the normal RTA substrate, the sarcin-ricin loop (SRL), and were not depurinated by RTA. An initial 80-nucleotide RNA ligand was minimized to a 31-nucleotide aptamer that contained all sequences and structures necessary for interacting with RTA. This minimal RNA formed high affinity complexes with RTA (K(d) = 7.3 nM) which could compete directly with the SRL for binding to RTA. The aptamer inhibited RTA depurination of the SRL and could partially protect translation from RTA inhibition. The IC(50) of the aptamer for RTA in an in vitro translation assay is 100 nM, roughly 3 orders of magnitude lower than a small molecule inhibitor of ricin, pteroic acid, and 2 orders of magnitude lower than the best known RNA inhibitor. The novel anti-RTA aptamers may find application as diagnostic reagents for a potential biological warfare agent and hold promise as scaffolds for the development of strong ricin inhibitors.
Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia (2017)

Chimeric antigen receptor (CAR)-redirected T lymphocytes are a promising immunotherapeutic approach and object of pre-clinical evaluation for the treatment of acute myeloid leukemia (AML). We developed a CAR against CD123, overexpressed on AML blasts and leukemic stem cells. However, potential recognition of low CD123-positive healthy tissues, through the on-target, off-tumor effect, limits safe clinical employment of CAR-redirected T cells. Therefore, we evaluated the effect of context-dependent variables capable of modulating CAR T cell functional profiles, such as CAR binding affinity, CAR expression, and target antigen density. Computational structural biology tools allowed for the design of rational mutations in the anti-CD123 CAR antigen binding domain that altered CAR expression and CAR binding affinity without affecting the overall CAR design. We defined both lytic and activation antigen thresholds, with early cytotoxic activity unaffected by either CAR expression or CAR affinity tuning but later effector functions impaired by low CAR expression. Moreover, the anti-CD123 CAR safety profile was confirmed by lowering CAR binding affinity, corroborating CD123 is a good therapeutic target antigen. Overall, full dissection of these variables offers suitable anti-CD123 CAR design optimization for the treatment of AML.
Analysis of Chemical Composition in Volatile Oil from Kalopanax septemlobus (Thunb.) Koidz.Root and Root Bark by GC-MS (2010)

[Objective]To analyze the compositions of volatile oil from root and root bark of Kalopanax septemlobus(Thunb.) Koidz.,so as to provide scientific evidence for the development of medicinal value of Kalopanax septemlobus(Thunb.) Koidz.[Method]The volatile compositions were extracted with headspace solid-phase micro-extraction(HS-SPME),and their contents and names were confirmed by GC-MS.[Result]Seventy-six and eighty-one compounds were separated and identified from the root bark and root of Kalopanax septemlobus(Thunb.) Koidz.,occupying 97.47% and 96.17% of total volatile oil respectively.The main components obtained from root and root bark of Kalopanax septemlobus(Thunb.) Koidz.were found to be similar,such as γ-elemene,trans-β-farnesene,α-Guaiene,alpha-Guaiene and 2-(1-methyl-ethyl)-5-methyl-phenol.It was also found that the contents of them in the two materials were not significant different.[Conclusion]The compounds and their relative content in root and its bark from Kalopanax septemlobus(Thunb.) Koidz.are confirmed in this study,which will provide scientific evidence for the development of the medicinal value of Kalopanax septemlobus(Thunb.) Koidz..
Evaluation of Models of Parkinson's Disease (2016)

Parkinson's disease is one of the most common neurodegenerative diseases. Animal models have contributed a large part to our understanding and therapeutics developed for treatment of PD. There are several more exhaustive reviews of literature that provide the initiated insights into the specific models; however a novel synthesis of the basic advantages and disadvantages of different models is much needed. Here we compare both neurotoxin based and genetic models while suggesting some novel avenues in PD modeling. We also highlight the problems faced and promises of all the mammalian models with the hope of providing a framework for comparison of various systems.
Occurrence of Severe Destructive Lyme Arthritis in Hamsters Vaccinated with Outer Surface Protein A and Challenged withBorrelia burgdorferi (2000)

Arthritis is a frequent and major complication of infection with Borrelia burgdorferi sensu stricto. The antigens responsible for the induction of arthritis are unknown. Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 microg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B. burgdorferi sensu stricto isolate 297 or C-1-11. Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 microg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection with B. burgdorferi sensu stricto. When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge with B. burgdorferi sensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged with B. burgdorferi sensu stricto. These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans.
Neuroprotective Activity of Peripherally Administered Liver Growth Factor in a Rat Model of Parkinson’s Disease (2013)

Liver growth factor (LGF) is a hepatic mitogen purified some years ago that promotes proliferation of different cell types and the regeneration of damaged tissues, including brain tissue. Considering the possibility that LGF could be used as a therapeutic agent in Parkinson's disease, we analyzed its potential neuroregenerative and/or neuroprotective activity when peripherally administered to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. For these studies, rats subjected to nigrostriatal lesions were treated intraperitoneally twice a week with LGF (5 microg/rat) for 3 weeks. Animals were sacrificed 4 weeks after the last LGF treatment. The results show that LGF stimulates sprouting of tyrosine hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine transporter expression, as well as dopamine levels in the denervated striatum of 6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor necrosis factor-alpha protein levels, which have been reported to have a role in neuroregeneration and neuroprotection. Besides, LGF stimulates the phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins which are critical for cell survival such as Bcl2 and Akt. Because LGF partially protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and reduces motor deficits in these animals, we propose LGF as a novel factor that may be useful in the treatment of Parkinson's disease.
A novel subset of human lymphocytes with a T cell receptor-gamma complex. (1987)

We have previously characterized a CD3+ T cell receptor (TCR) alpha/beta- human fetal cloned cell line, termed F6C7, which surface-expresses a CD3-associated gamma chain identified by anti-NKFi, an mAb with a restricted clonotypic reactivity. Here, we have produced an additional antibody, anti-Ti-gamma A, which recognizes a public epitope of the gamma molecule defined by anti-NKFi. Ti-gamma A is present on approximately 3% of circulating lymphocytes with a wide range (1-15%) among 30 healthy individuals tested. Two-color immunofluorescence experiments performed with anti-Ti-gamma A and BMA 031 mAb (a reagent specific for the TCR-alpha/beta receptor) showed that surface expression of Ti-alpha/beta and Ti-gamma A is mutually exclusive. Moreover, it was found that most Ti-gamma A+ cells are CD2+, CD3+, CD4-, CD5+, NKH1-, HLA class II-negative. In contrast, the expression of the CD8 molecule on these T lymphocytes appears to be variable from one individual to another. Finally, we found that Ti-gamma A+ cells represent a majority of peripheral lymphocytes that express CD3 proteins but not the TCR-alpha/beta heterodimer. The delineation of this unique lymphocyte subset should help further studies on the biology of cells with a CD3-associated gamma complex.
Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1A431E-associated familial Alzheimer's disease (2010)

SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF Abeta isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of Abeta1-37, Abeta1-38 and Abeta1-39; fragments that are normally produced by gamma-secretase, suggesting that the PSEN1 A431E mutation modulates gamma-secretase cleavage site preference in a disease-promoting manner.
UltraSPARC: the next generation superscalar 64-bit SPARC (2002)

UltraSPARC is the first microprocessor from Sun Microsystems' SPARC Technology Business to implement the new 64-bit SPARC V9 architecture. ULtraSPARC is equipped with unique multimedia capabilities and is capable of 4-way superscalar instruction dispatch, with an emphasis on maximal system efficiency and throughput in the execution of complex, memory-intensive applications. UltraSPARC maintains a strict binary compatibility with the thousands of existing 32-bit applications developed for other SPARC processors. This paper describes the feature set and operation of UItraSPARC.
Determination of sterols by capillary column gas chromatography. Differentiation among different types of olive oil: Virgin, refined, and solvent‐extracted (1996)

Abstract Compositional analysis of the sterol fraction of olive oil can be used to assess the degree of purity of the oil and the absence of admixture with other plant oils. This determination also permits characterization of the type of olive oil in question: virgin, refined, or solvent‐extracted. In the present work, 130 samples of olive oil were analyzed, the sterol fractions were separated from the unsaponifiable fraction by silica gel plate chromatography, and later they were analyzed as the trimethylsilyl ether derivatives by capillary column gas chromatography. From the results obtained, it was concluded that this methodology is able to differentiate among virgin, refined, and solvent‐extracted olive oils. Stigmasterol, clerosterol, Δ5‐avenasterol, Δ7‐stigmasterol, and Δ7‐avenasterol permit the differentiation of the three types of oil from one another. Campesterol, Δ5, 23‐stigmastadienol, β‐sitosterol, and Δ5,24‐stigmastadienol permit the differentiation of only two oils from each other but confirm the conclusions obtained for other sterols. Correlations between the different sterols of virgin, refined, and solven‐extracted olive oil also have been obtained.
Abnormal Behavior Associated with a Point Mutation in the Structural Gene for Monoamine Oxidase A (1993)

Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.
Monoclonal Antibodies to Human Respiratory Syncytial Virus and Their Use in Comparison of Different Virus Isolates (1984)

Monoclonal antibodies to the RSN -2 isolate of human respiratory syncytial (RS) virus have been characterized with regard to their specificity for viral polypeptides and for different RS virus isolates. Five hybridoma antibodies recognized the phospho-protein VPP32 and the other recognized the matrix protein VPM27 . Evidence was obtained to support the view that VPP32 was associated with the nucleoprotein VPN41 . Three of the antibodies to VPP32 showed cytoplasmic immunofluorescent staining while the other two showed only surface staining of virus-infected cells. The immunoblot technique was used to determine the immunoreactivity of four of the hybridoma antibodies against human RS isolates other than RSN -2. One of these antibodies reacted exclusively with RSN -2 virus isolate whereas the others detected determinants shared by all human RS isolates tested. Extension of this approach may offer the possibility of typing RS isolates using monoclonal antibodies.