gebhart/patrepeval huggingface dataset:
The HD mutation causes progressive lethal neurological disease in mice expressing reduced levels of huntingtin (2001)

Huntingtin is an essential protein that with mutant polyglutamine tracts initiates dominant striatal neurodegeneration in Huntington's disease (HD). To assess the consequences of mutant protein when huntingtin is limiting, we have studied three lines of compound heterozygous mice in which both copies of the HD gene homolog (Hdh) were altered, resulting in greatly reduced levels of huntingtin with a normal human polyglutamine length (Q20) and/or an expanded disease-associated segment (Q111): Hdh(neoQ20)/Hdh(neoQ20), Hdh(neoQ20)/Hdh(null) and Hdh(neoQ20)/Hdh(neoQ111). All surviving mice in each of the three lines were small from birth, and had variable movement abnormalities. Magnetic resonance micro-imaging and histological evaluation showed enlarged ventricles in approximately 50% of the Hdh(neoQ20)/Hdh(neoQ111) and Hdh(neoQ20)/Hdh(null) mice, revealing a developmental defect that does not worsen with age. Only Hdh(neoQ20)/Hdh(neoQ111) mice exhibited a rapidly progressive movement disorder that, in the absence of striatal pathology, begins with hind-limb clasping during tail suspension and tail stiffness during walking by 3-4 months of age, and then progresses to paralysis of the limbs and tail, hypokinesis and premature death, usually by 12 months of age. Thus, dramatically reduced huntingtin levels fail to support normal development in mice, resulting in reduced body size, movement abnormalities and a variable increase in ventricle volume. On this sensitized background, mutant huntingtin causes a rapid neurological disease, distinct from the HD-pathogenic process. These results raise the possibility that therapeutic elimination of huntingtin in HD patients could lead to unintended neurological, as well as developmental side-effects.
An Evolutionarily Conserved Enhancer Regulates Bmp4 Expression in Developing Incisor and Limb Bud (2012)

To elucidate the transcriptional regulation of Bmp4 expression during organogenesis, we used phylogenetic footprinting and transgenic reporter analyses to identify Bmp4 cis-regulatory modules (CRMs). These analyses identified a regulatory region located ∼46 kb upstream of the mouse Bmp4 transcription start site that had previously been shown to direct expression in lateral plate mesoderm. We refined this regulatory region to a 396-bp minimal enhancer, and show that it recapitulates features of endogenous Bmp4 expression in developing mandibular arch ectoderm and incisor epithelium during the initiation-stage of tooth development. In addition, this enhancer directs expression in the apical ectodermal ridge (AER) of the developing limb and in anterior and posterior limb mesenchyme. Transcript profiling of E11.5 mouse incisor dental lamina, together with protein binding microarray (PBM) analyses, allowed identification of a conserved DNA binding motif in the Bmp4 enhancer for Pitx homeoproteins, which are also expressed in the developing mandibular and incisor epithelium. In vitro electrophoretic mobility shift assays (EMSA) and in vivo transgenic reporter mutational analyses revealed that this site supports Pitx binding and that the site is necessary to recapitulate aspects of endogenous Bmp4 expression in developing craniofacial and limb tissues. Finally, Pitx2 chromatin immunoprecipitation (ChIP) demonstrated direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line. These results establish a direct molecular regulatory link between Pitx family members and Bmp4 gene expression in developing incisor epithelium.
Die Funktion des LIM-only Proteins 2 (FHL2) bei der Brustkrebsentstehung (2005)

Fragestellung: Das LIM-only Protein FHL2 ist in einer Vielzahl von Geweben bei der Tumorentstehung relevant. Im Rhabdomyosarkom ist es gegenüber Muskelvorläuferzellen herunterreguliert und als potentieller Tumorsuppressor von Bedeutung, in Hepatoblastomen wird FHL2 gegenüber gesundem Lebergewebe stark überexprimiert und ist ein potentielles Onkogen. Die Funktion von FHL2 im Mammakarzinom ist weitgehend unbekannt und wurde im Rahmen dieses Projektes charakterisiert.
IL-6: from its discovery to clinical applications (2010)

In the late 1960s, the essential role of T cells in antibody production was reported. This led to our hypothesis that T-cell-derived soluble factors would have to be involved in the activation of B cells. The factor that induced B cells to produce immunoglobulins was initially named B-cell stimulatory factor-2. In 1986, we successfully cloned the complementary DNA encoding B-cell stimulatory factor-2, now known as IL-6. At the same time, IFN-beta2 and a 26-kDa protein found in fibroblasts were independently cloned and found to be identical to IL-6. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte-stimulating factor were also proven to be the same molecule as IL-6. Now, we know that IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation and oncogenesis. Since the discovery of IL-6, we have further clarified its activities, the IL-6R system and the IL-6 signal transduction mechanism. On the basis of the findings, a new therapeutic approach to block the actions of IL-6 by use of a humanized anti-IL-6R antibody has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis and Castleman's disease. In this review, I discuss the history of IL-6 research as a paradigm of progress from basic science to clinical applications.
Comparison of Emissions and Efficiency of a Turbocharged Lean-Burn Natural Gas and Hythane-Fueled Engine (1997)

An experiment was conducted to evaluate the potential for reduced exhaust emissions and improved efficiency, by way of lean-burn engine fuelling with hydrogen supplemented natural gas (Hythane). The emissions and efficiency of the Hythane fuel (15 percent hydrogen, 85 percent natural gas by volume), were compared to the emissions and efficiency of pure natural gas using a turbocharged, spark ignition, 3.1 L, V-6 engine. The feasibility of heavy duty engine fueling with Hythane was assessed through testing conducted at engine speed and load combinations typical of heavy-duty engine operation. Comparison of the efficiency and emissions at MBT spark timing revealed that Hythane fueling of the test engine resulted in consistently lower brake specific energy consumption and emissions of total hydrocarbons (THC), carbon monoxide (CO), and carbon dioxide (CO2), at a given equivalence ratio. There was no clear trend with respect to MBT oxides of nitrogen (NOx) emissions. It was also discovered that an improved NOx-THC tradeoff resulted when Hythane was used to fuel the test engine. Consequently, Hythane engine operating parameters can be adjusted to achieve a concurrent reduction in NOx and THC emissions relative to natural gas fueling.
Immune Selection of Hot-Spot β2 -Microglobulin Gene Mutations, HLA-A2 Allospecificity Loss, and Antigen-Processing Machinery Component Down-Regulation in Melanoma Cells Derived from Recurrent Metastases following Immunotherapy (2005)

Scanty information is available about the mechanisms underlying HLA class I Ag abnormalities in malignant cells exposed to strong T cell-mediated selective pressure. In this study, we have characterized the molecular defects underlying HLA class I Ag loss in five melanoma cell lines derived from recurrent metastases following initial clinical responses to T cell-based immunotherapy. Point mutations in the translation initiation codon (ATG-->ATA) and in codon 31 (TCA-->TGA) of the beta(2)-microglobulin (beta(2)m) gene were identified in the melanoma cell lines 1074MEL and 1174MEL, respectively. A hot-spot CT dinucleotide deletion within codon 13-15 was found in the melanoma cell lines 1106MEL, 1180MEL, and 1259MEL. Reconstitution of beta(2)m expression restored HLA class I Ag expression in the five melanoma cell lines; however, the HLA-A and HLA-B,-C gene products were differentially expressed by 1074MEL, 1106MEL, and 1259MEL cells. In addition, in 1259MEL cells, the Ag-processing machinery components calnexin, calreticulin, and low m.w. polypeptide 10 are down-regulated, and HLA-A2 Ags are selectively lost because of a single cytosine deletion in the HLA-A2 gene exon 4. Our results in conjunction with those in the literature suggest the emergence of a preferential beta(2)m gene mutation in melanoma cells following strong T cell-mediated immune selection. Furthermore, the presence of multiple HLA class I Ag defects within a tumor cell population may reflect the accumulation of multiple escape mechanisms developed by melanoma cells to avoid distinct sequential T cell-mediated selective events.
The Extracellular Domain of Vaccinia Virus Protein B5R Affects Plaque Phenotype, Extracellular Enveloped Virus Release, and Intracellular Actin Tail Formation (1998)

Vaccinia virus produces two morphologically distinct forms of infectious virus, termed intracellular mature virus (IMV) and extracellular enveloped virus (EEV). EEV is important for virus dissemination within a host and has different surface proteins which bind to cell receptors different from those used by IMV. Six genes are known to encode EEV-specific proteins. One of these, B5R, encodes a 42-kDa glycoprotein with amino acid similarity to members of the complement control protein superfamily and contains four copies of a 50- to 70-amino-acid repeat called the short consensus repeat (SCR). Deletion of B5R causes a small-plaque phenotype, a 10-fold reduction in EEV formation, and virus attenuation in vivo. In this study, we inserted mutated versions of the B5R gene lacking different combinations of the SCRs into a virus deletion mutant lacking the B5R gene. The resultant viruses each formed small plaques only slightly larger than those of the deletion mutant; however, the virus containing only SCR 1 formed plaques slightly larger than those of viruses with SCRs 1 and 2 or SCRs 1, 2, and 3. All of these viruses produced approximately 50-fold more infectious EEV than wild-type virus and formed comet-shaped plaques under liquid overlay. Despite producing more EEV, the mutant viruses were unable to induce the polymerization of actin on intracellular virus particles. The implications of these results for our understanding of EEV formation, release, and infectivity are discussed.
The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress (1997)

These results suggest that this scoring system should prove to be a valuable instrument in helping to meet the many challenges offered by irritable bowel syndrome.
Direct writing of optical waveguides in fused silica by the fundamental beam of an Yb:KGW femtosecond laser (2021)

We report the fabrication of an optical waveguide with a propagation loss below 1 dB/cm in fused silica using the fundamental beam of an Yb:KGW femtosecond laser. By selecting the pulse energy and pulse duration, we obtained a propagation loss comparable with that of a waveguide made using a Ti:Sapphire laser. We demonstrate that the nano-wrinkles and nano-pores, which dominate the losses, are not formed in the modified silica if the pulse energy is below 0.80 μJ and the pulses are shorter than 300 fs.
Novel 3,6,7-Substituted Pyrazolopyrimidines as Positive Allosteric Modulators for the Hydroxycarboxylic Acid Receptor 2 (GPR109A) (2012)

A number of pyrazolopyrimidines were synthesized and tested for their positive allosteric modulation of the HCA(2) receptor (GPR109A). Compound 24, an efficacious and potent agonist and allosteric enhancer of nicotinic acid's action, was the basis for most other compounds. Interestingly, some of the compounds were found to increase the efficacy of the endogenous ligand 3-hydroxybutyrate and enhance its potency almost 10-fold. This suggests that the pyrazolopyrimidines may have therapeutic value when given alone.
A behavioral approach to worm detection (2004)

This paper presents a new approach to the automatic detection of worms using behavioral signatures. A behavioral signature describes aspects of any particular worm's behavior that are common across the manifestations of a given worm and that span its nodes in temporal order. Characteristic patterns of worm behaviors in network traffic include 1) sending similar data from one machine to the next, 2) tree-like propagation and reconnaissance, and 3) changing a server into a client. These behavioral signatures are presented within the context of a general worm propagation model. Taken together, they have the potential to detect entire classes of worms including those which have yet to be observed.
28.1: Distinguished Paper : A Novel Low‐Power‐Consumption All‐Digital System‐On‐Glass Display with Serial Interface (2009)

Abstract We have developed a low‐power LCD panel with a serial interface by combining the technique of integration of serial data receiver function and pixel memory circuits. It has achieved a low power consumption of 15uW in a 2.26‐inch format.
Inhibition of Human Neutrophil Elastase. 4. Design, Synthesis, X-ray Crystallographic Analysis, and Structure−Activity Relationships for a Series of P2-Modified, Orally Active Peptidyl Pentafluoroethyl Ketones (1998)

A series of P2-modified, orally active peptidic inhibitors of human neutrophil elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were designed using pentafluoroethyl ketone 1 as a model. Rational structural modifications were made at the P3, P2, and activating group (AG) portions of 1 based on structure-activity relationships (SAR) developed from in vitro (measured Ki) data and information provided by modeling studies that docked inhibitor 1 into the active site of HNE. The modeling-based design was corroborated with X-ray crystallographic analysis of the complex between 1 and porcine pancreatic elastase (PPE) and subsequently the complex between 1 and HNE.
Studies of Evolved Stars with a Mid-Infrared Interferometer (1998)

element stellar interferometer which employs heterodyne detection to gather starlight in the mid-infrared (9–12µm) wavelength range. Each element of the ISI is a 1.65m tele-scope, equipped with appropriate optical and detection systems. Successful operation of the ISI requires that the star image in each telescope be precisely centered on a signal detector. In order to accomplish this, near-infrared (2µm) guiding and tip-tilt correc-tion systems have been built and incorporated into the ISI telescopes. Each system uses an InSb infrared camera to determine small errors in the position of the source image. Slower fluctuations in position, occurring over a period of a few seconds, are corrected by adjusting the telescope tracking. Fast fluctuations are caused by the atmosphere, and are removed using a controllable tilting mirror. A significant improvement in signal quality, provided by this fast tip-tilt correction, is demonstrated by data taken on the supergiant α Orionis. To be suitable for study by the ISI, a source must have substantial mid-infrared flux. Evolved stars, typically very luminous and surrounded by one or more shells of dust, are the most common type of target for the ISI. The new guiding system enables the ISI to track these objects, which, because of their dust shells, often have insufficient visible flux for a guiding system using a silicon detector. During the 1997 observing
Human growth hormone in the blood of athymic mice grafted with cultures of hormone‐secreting human keratinocytes (1990)

An established line of human epidermal keratinocytes was permanently transformed by transfection with plasmid vectors bearing the human growth hormone gene under the control of two different promoters. Suitable selection permitted the isolation of clones secreting abundant growth hormone in culture. When such cultures were grafted to athymic mice, human growth hormone could be detected in the blood of the mice at concentrations in the physiological range for more than 4 weeks. Retrograde transfer from epithelial cells should be studied further as a possible means of introducing exogenous gene products into the circulation of humans.
A New Accelerated RC4 Scheme Using &#147;Ultra Gridsec&#148; and &#147;HIMAN&#148; and use this Scheme to Secure &#147;HIMAN&#148; Data (2009)

In most applications, security attributes are pretty difficult to meet but security becomes even a bigger challenge when talking about grid computing. Providing secure communication between elements of a computational grid, by encrypting data passes between them using enhanced encryption algorithms that do not affect the performance of the grid middleware completely comparable to the actual execution time. In this paper we will cover two points. First, accelerating RC4 encryption algorithm using our developed grid security scheme "ULTRA GRIDSEC" and our developed "HIMAN" middleware and show that RC4 was accelerated by about 873.52% comparable to that accelerated by "GRIDCRYPT" scheme that applied by "Alchemi" middleware developed by Melbourne University. Second, using the accelerated RC4 scheme to secure communication between elements of "HIMAN", the stream ciphering algorithms like RC4 are the most suitable encryption algorithms for applying inside "HIMAN" as we will show.
Pre-mRNA Secondary Structures Influence Exon Recognition (2007)

The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentally determined splicing enhancer and silencer motifs in their natural pre-mRNA context. We found that these splicing motifs are significantly more single-stranded than controls. These findings were validated by transfection experiments, where the effect of enhancer or silencer motifs on exon skipping was much more pronounced in single-stranded conformation. We also found that the structural context of predicted splicing motifs is under selection, suggesting a general importance of secondary structures on splicing and adding another level of evolutionary constraints on pre-mRNAs. Our results explain the action of mutations that affect splicing and indicate that the structural context of splicing motifs is part of the mRNA splicing code.
T-DNA as an Insertional Mutagen in Arabidopsis (1999)

Forward genetics begins with a mutant phenotype and asks the question “What is the genotype?” that is, what is the sequence of the mutant gene causing the altered phenotype? Reverse genetics begins with a mutant gene sequence and asks the question “What is the resulting change in phenotype
Regulation of the α-Galactosidase Activity in Streptococcus pneumoniae: Characterization of the Raffinose Utilization System (1999)

A 10.2-kb gene region was identified in the Streptococcus pneumoniae genome sequence that contains eight genes involved in regulation and metabolism of raffinose. The genes rafR and rafS are transcribed as one operon, and their gene products regulate the raffinose-dependent stimulation of a divergently transcribed second promoter (P(A)) directing the expression of aga, the structural gene for alpha-galactosidase. Raffinose-mediated transcription from P(A) results in a 500-fold increase in alpha-galactosidase activity in the cell. A third promoter within the cluster is responsible for the transcription of the remaining five genes (rafE, rafF, rafG, gtfA, and rafX), whose gene products might be involved in transport and metabolism of raffinose. The presence of additional internal promoters cannot be excluded. The aga promoter P(A) is negatively regulated by the presence of sucrose in the growth medium. Consistent with catabolite repression (CR), a DNA sequence with high homology to the CRE (cis-active element) was identified upstream of the aga promoter. Sucrose-mediated CR depends on the phosphoenolpyruvate: sucrose phosphotransferase system (PTS) but is unaffected by a mutation in a gene encoding a homolog of the CRE regulatory protein CcpA.
Comparison of the Short Test of Mental Status and the Mini-Mental State Examination in Mild Cognitive Impairment (2003)

Compared with the MMSE, the STMS was better able to document MCI and was more sensitive in detecting deficits in cognition in individuals who had normal cognition at baseline but later developed incident MCI or Alzheimer disease.
The role of gelatinase in hepatic metastasis of colorectal cancer. (2003)

Our data suggested that gelatinolytic activity in colorectal tumor tissues may facilitate the hepatic metastatic process in the steps after intravasation but not during or before intravasation.
O -Acetylation of Disialoganglioside GD 3 by Human Melanoma Cells Creates a Unique Antigenic Determinant (1984)

Monoclonal antibody Mab D1.1 recognizes on human melanoma cells a ganglioside antigen characterized by an alkali-labile O-acetylated sialic acid residue. Immunochemical analysis showed that this molecule is an O-acetylated product of the neuroectoderm-associated disialoganglioside GD3. Controlled chemical O-acetylation of purified GD3 resulted in the generation of this same epitope. Lysates of human melanoma cells were found to contain O-acetyltransferase activity capable of generating the antigenic epitope recognized by Mab D1.1. Thus, the addition of a single O-acetyl group to a common cell surface-associated ganglioside can create a potentially tumor-specific antigen.
Amniotic Membrane as a Living Surgical Dressing in Human Patients (1973)

Preliminary observations on the role of the amniotic membrane devoid of the chorion have been made. Clinical cases have been presented to illustrate that this membrane as an allograft may have a potential application in surgery. Autograft studies are pursued in our laboratory and shown promise. These results will be reported.
Differential TLR activation of murine mesenchymal stem cells generates distinct immunomodulatory effects in EAE (2016)

Taken together, these data show that pretreatment of MSCs with poly(I:C) improved their immunosuppressive abilities. This may provide an opportunity to better define strategies for cell-based therapies to autoimmune diseases.
2-(tert.amino)-11-(4-methylpiperazino)dibenzo[b,f]thiepins and their 10,11-dihydro derivatives; Synthesis and neuroleptic activity (1987)

Reactions of (2-iodophenyl)acetic acid with 4-(dimethylamino)thiophenol, 4-piperidinothiophenol, and 4-morpholinothiophenol in boiling aqueous potassium hydroxide solutions in the presence of copper gave the arylacetic acids IVabc which were cyclized with polyphosphoric acid at 130 °C to 8-(tert.amino)dibenzo[ b,f ]thiepin-10(11 H )-ones Vabc . The following reactions with 1-methylpiperazine in boiling benzene in the presence of titanium tetrachloride afforded the enamines IIabc . Compounds IIa and IIc were reduced with diborane to the 10,11-dihydro compounds Ia and Ic . Compound Ia (the 8-dimethylamino derivative of perathiepin) is a typical incisive neuroleptic agent with very strong cataleptic, antiapomorphine, central depressant, and antiadrenergic activities. The morpholino derivative Ic and the enamines IIb and IIc are less active.