gebhart/patrepeval huggingface dataset:
The HLA genomic loci map: expression, interaction, diversity and disease (2009)

The human leukocyte antigen (HLA) super-locus is a genomic region in the chromosomal position 6p21 that encodes the six classical transplantation HLA genes and at least 132 protein coding genes that have important roles in the regulation of the immune system as well as some other fundamental molecular and cellular processes. This small segment of the human genome has been associated with more than 100 different diseases, including common diseases, such as diabetes, rheumatoid arthritis, psoriasis, asthma and various other autoimmune disorders. The first complete and continuous HLA 3.6 Mb genomic sequence was reported in 1999 with the annotation of 224 gene loci, including coding and non-coding genes that were reviewed extensively in 2004. In this review, we present (1) an updated list of all the HLA gene symbols, gene names, expression status, Online Mendelian Inheritance in Man (OMIM) numbers, including new genes, and latest changes to gene names and symbols, (2) a regional analysis of the extended class I, class I, class III, class II and extended class II subregions, (3) a summary of the interspersed repeats (retrotransposons and transposons), (4) examples of the sequence diversity between different HLA haplotypes, (5) intra- and extra-HLA gene interactions and (6) some of the HLA gene expression profiles and HLA genes associated with autoimmune and infectious diseases. Overall, the degrees and types of HLA super-locus coordinated gene expression profiles and gene variations have yet to be fully elucidated, integrated and defined for the processes involved with normal cellular and tissue physiology, inflammatory and immune responses, and autoimmune and infectious diseases.
The progressive tactile hyperalgesia induced by peripheral inflammation is nerve growth factor dependent (1997)

Experimental peripheral inflammation results in cutaneous mechanical hypersensitivity, and repeated low intensity mechanical stimulation of the inflamed skin induces a progressively incrementing hyperalgesia. We have now examined whether the elevation in nerve growth factor (NGF) induced by the inflammation contributes to this progressive hyperalgesia. An i.p. injection of anti-NGF antiserum (5 microliters g-1) 1 h before induction of inflammation by intraplantar complete Freund's adjuvant (CFA) injection and 24 h after, both reduced the basal inflammatory hypersensitivity and significantly attenuated the progressive increase of spontaneous activity, touch-, pinch- and A beta-afferent-evoked responses, and the progressive reduction of the mechanical threshold of biceps femoris/semitendinosus alpha motoneurones normally evoked by repeated (every 5 min) tactile stimulation of the inflamed hindpaw, in decerebrate-spinal rats. NGF contributes, therefore, to the progressive tactile hyperalgesia elicited by repeated touch stimulation of inflamed tissue.
Transforming growth factor alpha: a promoter of motoneuron survival of potential biological relevance. (2001)

Expression of transforming growth factor alpha (TGFalpha), a member of the epidermal growth factor (EGF) family, is a general response of adult murine motoneurons to genetic and experimental lesions, TGFalpha appearing as an inducer of astrogliosis in these situations. Here we address the possibility that TGFalpha expression is not specific to pathological situations but may participate to the embryonic development of motoneurons. mRNA of TGFalpha and its receptor, the EGF receptor (EGFR), were detected by ribonuclease protection assay in the ventral part of the cervical spinal cord from embryonic day 12 (E12) until adult ages. Reverse transcription-PCR amplification of their transcripts from immunopurified E15 motoneurons, associated with in situ double-immunohistological assays, identified embryonic motoneurons as cellular sources of the TGFalpha-EGFR couple. In vitro, TGFalpha promoted the survival of immunopurified E15 motoneurons in a dose-dependent manner, with a magnitude similar to BDNF neuroprotective effects at equivalent concentrations. In a transgenic mouse expressing a human TGFalpha transgene under the control of the metallothionein 1 promoter, axotomy of the facial nerve provoked significantly less degeneration in the relevant motor pool of 1-week-old mice than in wild-type animals. No protection was observed in neonates, when the transgene exhibits only weak expression levels in the brainstem. In conclusion, our results point to TGFalpha as a physiologically relevant candidate for a neurotrophic role on developing motoneurons. Its expression by the embryonic motoneurons, which also synthesize its receptor, suggests that this chemokine is endowed with the capability to promote motoneuron survival in an autocrine-paracrine manner.
Comparison of Urticaria Activity Score Over 7 Days (UAS7) Values Obtained from Once-Daily and Twice-Daily Versions: Results from the ASSURE-CSU Study (2018)

The once- and twice-daily UAS7 scores were highly consistent, supporting the use of either version when evaluating CSU activity.
The primary structure of NG2, a novel membrane-spanning proteoglycan. (1991)

The complete primary structure of the core protein of rat NG2, a large, chondroitin sulfate proteoglycan expressed on O2A progenitor cells, has been determined from cDNA clones. These cDNAs hybridize to an mRNA species of 8.9 kbp from rat neural cell lines. The total contiguous cDNA spans 8,071 nucleotides and contains an open reading frame for 2,325 amino acids. The predicted protein is an integral membrane protein with a large extracellular domain (2,224 amino acids), a single transmembrane domain (25 amino acids), and a short cytoplasmic tail (76 amino acids). Based on the deduced amino acid sequence and immunochemical analysis of proteolytic fragments of NG2, the extracellular region can be divided into three domains: an amino terminal cysteine-containing domain which is stabilized by intrachain disulfide bonds, a serine-glycine-containing domain to which chondroitin sulfate chains are attached, and another cysteine-containing domain. Four internal repeats, each consisting of 200 amino acids, are found in the extracellular domain of NG2. These repeats contain a short sequence that resembles the putative Ca(++)-binding region of the cadherins. The sequence of NG2 does not show significant homology with any other known proteins, suggesting that NG2 is a novel species of integral membrane proteoglycan.
Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection (2013)

HIV-1 entry into CD4(+) T cells requires binding of the virus to CD4 followed by engagement of either the C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4) coreceptor. Pharmacologic blockade or genetic inactivation of either coreceptor protects cells from infection by viruses that exclusively use the targeted coreceptor. We have used zinc-finger nucleases to drive the simultaneous genetic modification of both ccr5 and cxcr4 in primary human CD4(+) T cells. These gene-modified cells proliferated normally and were resistant to both CCR5- and CXCR4-using HIV-1 in vitro. When introduced into a humanized mouse model of HIV-1 infection, these coreceptor negative cells engraft and traffic normally, and are protected from infection with CCR5- and CXCR4-using HIV-1 strains. These data suggest that simultaneous disruption of the HIV coreceptors may provide a useful approach for the long-term, drug-free treatment of established HIV-1 infections.
Authoritarianism in the new states of Central Asia: an overview of post-independence politics (1996)

'Nach dem Zusammenbruch der UdSSR erwartete man, daß sich die neuen unabhängigen Staaten Zentralasiens als instabil und anfällig für Gewalt erweisen würden, doch haben vier Jahre Unabhängigkeit gezeigt, daß sie, mit der Ausnahme Tadschikistans, zu den stabilsten der sowjetischen Nachfolgestaaten gehören. Diejenigen der zentralasiatischen Führer, die den Erhalt der politischen und gesellschaftlichen Stabilität für wichtiger halten, fühlen sich in ihrer Wahl bestätigt. Die Präsidenten Kasachstans und Kirgisiens, die eine Demokratisierung versucht haben, wurden ihrerseits zunehmend autoritärer, um die Reformprogramme durchsetzen zu können. Die Notwendigkeit der Stabilität wird dadurch begründet, daß es Zentralasien an Erfahrung mit der Demokratie westlichen Stils mangelt und in der Region keine Tradition der Staatlichkeit existiert, obwohl die politische und kulturelle Oberschicht dort auch schon vor der Auflösung der UdSSR ein gut entwickeltes nationales Bewußtsein besaß. Westliche Beobachter, die darauf gehofft hatten, daß die Demokratie in Kasachstan und Kirgisien rasch Wurzeln schlagen würde, sahen sich enttäuscht, als die Präsidenten dieser Länder immer autokratischer regierten. Gleichzeitig wuchs das Interesse an Usbekistan trotz beträchtlicher Demokratiedefizite in einem Maße, wie der Westen die strategische Bedeutung dieses Landes erkannte.' (Autorenreferat)
Dissecting the human peripheral B‐cell compartment with phage display‐derived antibodies (1999)

Previously we have employed a large semisynthetic phage antibody display library, in combination with subtractive selection by flow cytometry to isolate phage antibodies specific for subpopulations of leucocytes. In this study, human tonsillar B cells were incubated with the phage library and IgD- CD38- memory B lymphocytes and attached phage antibodies were selected by cell sorting. In a panel of 17 monoclonal phage antibodies obtained, five displayed binding to cells of multiple haematopoietic lineages or broadly reacted with B-lineage cells. Immunofluorescent, immunohistochemical and biochemical studies permitted the characterization of the target molecules recognized by these phage antibodies. The remaining 12 antibodies displayed restricted binding to small subpopulations of peripheral human B cells. These results show that subtractive selections with phage antibody display libraries in combination with flow cytometry yield antibodies that bind to differentially expressed molecules on closely related cell populations, and can be used as a tool in a variety of assays.
Requirement of the Yeast RTH1 5′ to 3′ Exonuclease for the Stability of Simple Repetitive DNA (1995)

Simple repetitive DNA sequences are unstable in human colorectal cancers and a variety of other cancers. Mutations in the DNA mismatch repair genes MSH2, MLH1, and PMS1 result in elevated rates of spontaneous mutation and cause a marked increase in the instability of simple repeats. Compared with the wild type, a null mutation in the yeast RTH1 gene, which encodes a 5' to 3' exonuclease, was shown to increase the rate of instability of simple repetitive DNA by as much as 280 times and to increase the spontaneous mutation rate by 30 times. Epistasis analyses were consistent with the hypothesis that this RTH1-encoded nuclease has a role in the MSH2-MLH-1-PMS1 mismatch repair pathway.
Transgenic mouse brain histopathology resembles early Alzheimer's disease (1994)

Transgenic mice expressing the 751-amino acid form of the human amyloid precursor protein develop extracellular beta-amyloid protein (A beta)-immunoreactive deposits that increase in frequency with age. Here we show that the appearance and histological profile of deposits in the transgenic mice closely resemble those of preamyloid deposits in the brains of young adults with Down's syndrome, who presumably have the pathology of early-stage Alzheimer's disease. Specific monoclonal antibodies reveal that material in the deposits has the free carboxyl terminus of A beta 1-42, and that the deposits contain material which, by immunohistochemical analysis, apparently originates from the human beta-amyloid precursor protein (beta PP) transgene. In rare cases, the transgenic mouse brains contain several different histopathological characteristics of Alzheimer lesions. These features include dense A beta immunoreactivity which co-localizes with gliosis and with Alz50-immunoreactive structures resembling swollen boutons of dystrophic neurites. These observations demonstrate that the murine brain is capable of reproducing several typical features of Alzheimer histopathology.
Microbial production of plant benzylisoquinoline alkaloids (2008)

Benzylisoquinoline alkaloids, such as the analgesic compounds morphine and codeine, and the antibacterial agents berberine, palmatine, and magnoflorine, are synthesized from tyrosine in the Papaveraceae, Berberidaceae, Ranunculaceae, Magnoliaceae, and many other plant families. It is difficult to produce alkaloids on a large scale under the strict control of secondary metabolism in plants, and they are too complex for cost-effective chemical synthesis. By using a system that combines microbial and plant enzymes to produce desired benzylisoquinoline alkaloids, we synthesized (S)-reticuline, the key intermediate in benzylisoquinoline alkaloid biosynthesis, from dopamine by crude enzymes from transgenic Escherichia coli. The final yield of (S)-reticuline was 55 mg/liter within 1 h. Furthermore, we synthesized an aporphine alkaloid, magnoflorine, or a protoberberine alkaloid, scoulerine, from dopamine via reticuline by using different combination cultures of transgenic E. coli and Saccharomyces cerevisiae cells. The final yields of magnoflorine and scoulerine were 7.2 and 8.3 mg/liter culture medium. These results indicate that microbial systems that incorporate plant genes cannot only enable the mass production of scarce benzylisoquinoline alkaloids but may also open up pathways for the production of novel benzylisoquinoline alkaloids.
Hepatocyte Growth Factor Induces Proliferation of Lens Epithelial Cells through Activation of ERK1/2 and JNK/SAPK (2004)

The data indicate that HGF is a potent growth factor for LECs and may contribute to the development of PCO and suggest that the signaling pathways involved in HGF-stimulated proliferation may constitute potential therapeutic targets in the treatment of PCO.
The Proteolytic Fragments of the Alzheimer's Disease-associated Presenilin-1 Form Heterodimers and Occur as a 100–150-kDa Molecular Mass Complex (1998)

Mutations in the presenilin (PS) genes are linked to early onset familial Alzheimer's disease (FAD). PS-1 proteins are proteolytically processed by an unknown protease to two stable fragments of approximately 30 kDa (N-terminal fragment (NTF)) and approximately 20 kDa (C-terminal fragment (CTF)) (Thinakaran, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., Ratovitsky, T., Davenport, F., Nordstedt, C., Seeger, M., Hardy, J., Levey, A. I., Gandy, S. E., Jenkins, N. A., Copeland, N. G., Price, D. L., and Sisodia, S. S. (1996) Neuron 17, 181-190). Here we show that the CTF and NTF of PS-1 bind to each other. Fractionating proteins from 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid-extracted membrane preparations by velocity sedimentation reveal a high molecular mass SDS and Triton X-100-sensitive complex of approximately 100-150 kDa. To prove if both proteolytic fragments of PS-1 are bound to the same complex, we performed co-immunoprecipitations using multiple antibodies specific to the CTF and NTF of PS-1. These experiments revealed that both fragments of PS-1 occur as a tightly bound non-covalent complex. Upon overexpression, unclipped wild type PS-1 sediments at a lower molecular weight in glycerol velocity gradients than the endogenous fragments. In contrast, the non-cleavable, FAD-associated PS-1 Deltaexon 9 sediments at a molecular weight similar to that observed for the endogenous proteolytic fragments. This result may indicate that the Deltaexon 9 mutation generates a mutant protein that exhibits biophysical properties similar to the naturally occurring PS-1 fragments. This could explain the surprising finding that the Deltaexon 9 mutation is functionally active, although it cannot be proteolytically processed (Baumeister, R., Leimer, U., Zweckbronner, I., Jakubek, C., Grünberg, J., and Haass, C. (1997) Genes & Function 1, 149-159; Levitan, D., Doyle, T., Brousseau, D., Lee, M., Thinakaran, G., Slunt, H., Sisodia, S., and Greenwald, I. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 14940-14944). Formation of a high molecular weight complex of PS-1 composed of both endogenous PS-1 fragments may also explain the recent finding that FAD-associated mutations within the N-terminal portion of PS-1 result in the hyperaccumulation not only of the NTF but also of the CTF (Lee, M. K., Borchelt, D. R., Kim, G., Thinakaran, G., Slunt, H. H., Ratovitski, T., Martin, L. J., Kittur, A., Gandy, S., Levey, A. I., Jenkins, N., Copeland, N., Price, D. L., and Sisodia, S. S. (1997) Nat. Med. 3, 756-760). Moreover, these results provide a model to understand the highly regulated expression and processing of PS proteins.
Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene (2003)

Most sporadic colon adenomas acquire mutations in the adenomatous polyposis coli gene (APC) and show defects in APC-dependent signaling. APC influences the expression of several genes, including the c-myc oncogene and its antagonist Mad1. Ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is a transcriptional target of c-myc and a modifier of APC-dependent tumorigenesis. A single-nucleotide polymorphism exists in intron 1 of the human ODC gene, which lies between two myc-binding domains. This region is known to affect ODC transcription, but no data exist on the relationship of this polymorphism to risk of colorectal neoplasia in humans. We show that individuals homozygous for the minor ODC A-allele who reported using aspirin are approximately 0.10 times as likely to have an adenoma recurrence as non-aspirin users homozygous for the major G-allele. Mad1 selectively suppressed the activity of the ODC promoter containing the A-allele, but not the G-allele, in a human colon cancer-derived cell line (HT29). Aspirin (>or=10 microM) did not affect ODC allele-specific promoter activity but did activate polyamine catabolism and lower polyamine content in HT29 cells. We propose that the ODC polymorphism and aspirin act independently to reduce the risk of adenoma recurrence by suppressing synthesis and activating catabolism, respectively, of colonic mucosal polyamines. These findings confirm the hypothesis that the ODC polymorphism is a genetic marker for colon cancer risk, and support the use of ODC inhibitors and aspirin, or other nonsteroidal antiinflammatory drugs (NSAIDs), in combination as a strategy for colon cancer prevention.
A Tyrosine Kinase Created by Fusion of the PDGFRA and FIP1L1 Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome (2003)

The hypereosinophilic syndrome may result from a novel fusion tyrosine kinase - FIP1L1-PDGFRalpha - that is a consequence of an interstitial chromosomal deletion. The acquisition of a T674I resistance mutation at the time of relapse demonstrates that FIP1L1-PDGFRalpha is the target of imatinib. Our data indicate that the deletion of genetic material may result in gain-of-function fusion proteins.
Clinical oncology : a multidisciplinary approach for physicians and students (1993)

Statement of the Clinical Oncologic Problem / The Biology of Cancer / The Pathology of Cancer / Principles of Surgical Oncology / Basic Principles of Radiobiology / Principles of Radiation Oncology and Cancer Radiotherapy / Basic Concepts in Radiation Physics / Basic Concepts of Cancer Chemotherapy and Principles of Medical Oncology / Basic Concepts in Investigational Therapeutics and Clinical Trials / Gene Therapy for Malignancy / Basic Concepts of Tumor Immunology and Principles of Immunotherapy / AIDS / Oncologic Emergencies / Principles of Psychosocial Oncology / Principles of Oncologic Imaging and Tumor Imaging / Skin Cancer / Breast Cancer / Malignant Lymphomas / Pediatric Solid Tumors / Tumors of the Head and Neck / Gynecologic Tumors / Urologic and Male Genital Cancers / The Leukemias / Soft Tissue Sarcomas / Bone Tumors / Cancer of the Endocrine Glands: Thyroid, Adrenal and Pituitary / Alimentary Cancer / Cancer of the Major Digestive Glands: Pancreas, Liver, Bile Ducts, Gall Bladder / Central Nervous System Tumors / Lung Cancer / Metastases and Disseminated Diseases / Basic and Advanced Methods of Pain Control / Palliative Care / Late Effects of Cancer Treatment Radiation & Drug Therapy.
ProfileMe: hardware support for instruction-level profiling on out-of-order processors (1997)

Profile data is valuable for identifying performance bottlenecks and guiding optimizations. Periodic sampling of a processor's performance monitoring hardware is an effective, unobtrusive way to obtain detailed profiles. Unfortunately, existing hardware simply counts events, such as cache misses and branch mispredictions, and cannot accurately attribute these events to instructions, especially on out-of-order machines. We propose an alternative approach, called ProfileMe, that samples instructions. As a sampled instruction moves through the processor pipeline, a detailed record of all interesting events and pipeline stage latencies is collected. ProfileMe also supports paired sampling, which captures information about the interactions between concurrent instructions, revealing information about useful concurrency and the utilization of various pipeline stages while an instruction is in flight. We describe an inexpensive hardware implementation of ProfileMe, outline a variety of software techniques to extract useful profile information from the hardware, and explain several ways in which this information can provide valuable feedback for programmers and optimizers.
Identification and characterization of the multigene family encoding 44-kDa major outer memberane proteins of the Human Granulocytic Ehrlichiosis Agent / (2000)

Human granulocytic ehrlichiosis (HGE), an emerging tick bone zoonosis is caused by a gram-negative obligatory intracellular bacterium called the HGE agent.Comparison o f 16S rRNA gene sequences indicates that that the HGE agent is a new strain o f E. phagocytophila or E. equi, which belongs to the family Rickettsiaceae.Since the HGE agent is a newly identified human pathogen, we know little about the genetics, immune recognition, and pathogenesis o f this ehrlichial organism.This study attempted to view the molecular determinants of the corresponding host parasite interaction and adaptation during the transmission.First, we have identified a multigene family encoding 44-kDa major outer membrane proteins o f the HGE agent.The genetic organization, distribution and gene structme ofp44-gene family were investigated.Otn results show that the /?44-gene family consists o f at least 21 homologous genes that either individually located or formed a cluster o f two or three in the genome.Comparison o f amino acid sequences indicates that P44 homologs shared a common protein structure, a single central hypervariable region flanked by N-and C-terminal conserved regions.Second, the expression of/7-/4-multigene family during the tick transmission and in the cell cultures at different temperature are analyzed by the RT-PCR, Northern blot, and Western blot analysis.We foimd that p44-gene family was differentially expressed during the tick transmission or in the cell culture at different temperature.The /?44-homologous 4.4.5 Aligment o f amino acid sequences deduced from cDNA clones and the corresponding homologous genes o f the HGE agent.........