gebhart/patrepeval huggingface dataset:
Streptococcal cell wall-induced arthritis: requirements for IL-4, IL-10, IFN-gamma, and monocyte chemoattractant protein-1. (1998)

Intra-articular injection of streptococcal cell wall Ag followed by i.v. challenge ("reactivation") results in a destructive lymphocyte-dependent monoarticular arthritis. To further define the role of immune mechanisms in the model, Abs to Th1 and Th2-related cytokines were evaluated. Treatment of rats with antibodies to IL-4 reduced swelling, while treatment with anti-IL-10 or anti-IFN-gamma either had no effect or slightly enhanced the inflammatory response. These results suggest that Th-2 immune mechanisms may be, at least in part, operative in the model. To more precisely define the role of IL-4, the effects of anti-IL-4 on monocyte chemoattractant protein-1 (MCP-1) expression were evaluated. Initial studies demonstrated that mRNA (as determined by in situ hybridization) and protein (as determined by immunofluorescence) for MCP-1 were detectable in inflamed synovial tissue in a time-dependent manner. Anti-IL-4 treatment significantly reduced the expression of mRNA for MCP-1 24 and 72 h after reactivation. In addition, anti-MCP-1 inhibited swelling and reduced influx of (111)In-labeled T cells. These data suggest that the reactivation model of streptococcal cell wall Ag-induced arthritis is Th-2 dependent, and that an inter-relationship exists between IL-4 and the expression of MCP-1.
Benchmark tests for the DARPA Spoken Language Program (1993)

This paper documents benchmark tests implemented within the DARPA Spoken Language Program during the period November, 1992 - January, 1993. Tests were conducted using the Wall Street Journal-based Continuous Speech Recognition (WSJ-CSR) corpus and the Air Travel Information System (ATIS) corpus collected by the Multi-site ATIS Data COllection Working (MADCOW) Group. The WSJ-CSR tests consist of tests of large vocabulary (lexicons of 5,000 to more than 20,000 words) continuous speech recognition systems. The ATIS tests consist of tests of (1) ATIS-domain spontaneous speech (lexicons typically less than 2,000 words), (2) natural language understanding, and (3) spoken language understanding. These tests were reported on and discussed in detail at the Spoken Language Systems Technology Workshop held at the Massachusetts Institute of Technology, January 20-22, 1993.
Molecular recognition of pathogen attack occurs inside of plant cells in plant disease resistance specified by the Arabidopsis genes RPS2  and  RPM1 (1996)

The Arabidopsis thaliana disease resistance genes RPS2 and RPM1 belong to a class of plant disease resistance genes that encode proteins that contain an N-terminal tripartite nucleotide binding site (NBS) and a C-terminal tandem array of leucine-rich repeats. RPS2 and RPM1 confer resistance to strains of the bacterial phytopathogen Pseudomonas syringae carrying the avirulence genes avrRpt2 and avrB, respectively. In these gene-for-gene relationships, it has been proposed that pathogen avirulence genes generate specific ligands that are recognized by cognate receptors encoded by the corresponding plant resistance genes. To test this hypothesis, it is crucial to know the site of the potential molecular recognition. Mutational analysis of RPS2 protein and in vitro translation/translocation studies indicated that RPS2 protein is localized in the plant cytoplasm. To determine whether avirulence gene products themselves are the ligands for resistance proteins, we expressed the avrRpt2 and avrB genes directly in plant cell using a novel quantitative transient expression assay, and found that expression of avrRpt2 and avrB elicited a resistance response in plants carrying the corresponding resistance genes. This observation indicates that no bacterial factors other than the avirulence gene products are required for the specific resistance response as long as the avirulence gene products are correctly localized. We propose that molecular recognition of P. syringae in RPS2- and RPM1-specified resistance occurs inside of plant cells.
Traditional and New Influenza Vaccines (2013)

The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a "universal" influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets.
Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease (2009)

Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease.
The anti-human tumor effect and generation of human cytotoxic T cells in SCID mice given human peripheral blood lymphocytes by the in vivo transfer of the Interleukin-6 gene using adenovirus vector. (1997)

Interleukin-6 (IL-6) was found to function as a late-acting killer helper factor in the differentiation of CTLs. In the model of tumor-bearing mice, the systemic administration of recombinant IL-6 was found to mediate the antitumor effect on the immunogenic murine tumors via the in vivo induction of murine CTLs but not on the poorly immunogenic murine tumors in our previous study. However, an in vivo experimental model capable of analyzing the anti-human tumor effect via the in vivo induction of human CTLs has not yet been established. Therefore, in the present study, severe combined immunodeficient mice were given human peripheral blood lymphocytes (SCID-PBL/hu), and thereafter human tumor cells were administered i.p. into these SCID-PBL/hu mice as a model of human patients with cancer. When these SCID-PBL/hu mice bearing allogeneic human CESS B blastoid tumor cells were treated in vivo with recombinant adenovirus vector expressing IL-6 cDNA, both the induction of CD8+ human CTLs against CESS cells in the spleen cells and peritoneal exudate cells and a prolongation in the survival of these mice were observed. Furthermore, SCID-PBL/hu mice were given peripheral blood lymphocytes from patients with cancer (gastric or rectal cancers) and autologous human tumor cells. The in vivo administration of recombinant adenovirus vector expressing IL-6 cDNA induced CD8+ human CTLs specific for autologous human tumor cells from human precursor T cells. The in vivo injection of the IL-6 gene also inhibited growth and metastasis in autologous human cancers. Based on the above findings, the experimental model using SCID-PBL/hu mice and the IL-6 gene delivered in vivo by an adenovirus vector might therefore provide a new strategy capable of analyzing an anti-human tumor effect and the in vivo induction of human CTLs by cytokine gene therapy without using the human body.
Antibody responses to the 18-kDa protein of Mycobacterium leprae in leprosy and tuberculosis patients. (1992)

The 18-kDa protein of Mycobacterium leprae, as recognized by the monoclonal antibody L5, has a restricted species distribution, being confined to M. leprae and M. habana. We have developed a solid-phase ELISA using purified, recombinant M. leprae 18-kDa protein and compared the serological responses of Nepali leprosy and tuberculosis patients and endemic control subjects to the protein and the M. leprae phenolic glycolipid-I (PGL-I). Few control subjects had anti-18-kDa antibodies. A small proportion of paucibacillary (PB) leprosy and 42% of multibacillary (MB) leprosy patients had IgG anti-M. leprae antibodies. A similar proportion (47%) of Nepali tuberculosis (TB) patients were seropositive, and IgG anti-18-kDa antibody levels were significantly higher in MB and TB patients than in control subjects. By comparison, IgM anti-PGL-I antibodies were detected in 88% of MB leprosy patients and only 7% of TB patients. The possible reasons for the 18-kDa protein seroreactivity in TB patients are discussed, and the anti-18-kDa assay is compared with other antibody assays for protein and nonprotein antigens of M. leprae. It is concluded that the sensitivity and specificity of the anti-M. leprae 18-kDa ELISA are insufficient for the assay to be of clinical utility in leprosy patients.
The Impact of Ischemia Time During Open Nephron Sparing Surgery on Solitary Kidneys: A Multi-Institutional Study (2007)

Vascular clamping during open nephron sparing surgery is associated with a higher incidence of renal complications. Attempts to limit warm ischemia to 20 minutes and cold ischemia to 35 minutes should be used when vascular clamping is necessary.
Sensitivity of near-infrared spectroscopy and diffuse correlation spectroscopy to brain hemodynamics: simulations and experimental findings during hypercapnia (2014)

Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) are two diffuse optical technologies for brain imaging that are sensitive to changes in hemoglobin concentrations and blood flow, respectively. Measurements for both modalities are acquired on the scalp, and therefore hemodynamic processes in the extracerebral vasculature confound the interpretation of cortical hemodynamic signals. The sensitivity of NIRS to the brain versus the extracerebral tissue and the contrast-to-noise ratio (CNR) of NIRS to cerebral hemodynamic responses have been well characterized, but the same has not been evaluated for DCS. This is important to assess in order to understand their relative capabilities in measuring cerebral physiological changes. We present Monte Carlo simulations on a head model that demonstrate that the relative brain-to-scalp sensitivity is about three times higher for DCS (0.3 at 3 cm) than for NIRS (0.1 at 3 cm). However, because DCS has higher levels of noise due to photon-counting detection, the CNR is similar for both modalities in response to a physiologically realistic simulation of brain activation. Even so, we also observed higher CNR of the hemodynamic response during graded hypercapnia in adult subjects with DCS than with NIRS.
Purification of a RecA protein analogue from Bacillus subtilis. (1985)

We have identified in Bacillus subtilis an analogue of the Escherichia coli RecA protein. Its activities suggest that it has a corresponding role in general genetic recombination and in regulation of SOS (DNA repair) functions. The B. subtilis protein (B. subtilis Rec) has a Mr of 42,000 and cross-reacts with antisera raised against E. coli RecA protein. Its level is significantly reduced in the recombination-deficient recE4 mutant. B. subtilis Rec is induced 10- to 20-fold in rec+ strains following treatment with mitomycin C, whereas it is not induced in the recombination-deficient mutants recE4, recE45, and recA1. We have purified B. subtilis Rec about 2000-fold to near homogeneity and we describe its activities. It catalyzes DNA-dependent hydrolysis of dATP at a rate comparable to that of E. coli RecA protein. However, B. subtilis Rec has a negligible ATPase activity, although ATP effectively inhibits dATP hydrolysis. In the presence of dATP, B. subtilis Rec catalyzes DNA strand transfer, assayed by the conversion of phi X174 linear duplex DNA and homologous circular single-stranded DNA to replicative form II (circular double-stranded DNA with a discontinuity in one strand). ATP does not support strand transfer by this protein. B. subtilis Rec catalyzes proteolytic cleavage of E. coli LexA repressor in a reaction that requires single-stranded DNA and nucleoside triphosphate. This result suggests that an SOS regulatory system like the E. coli system is present in B. subtilis. The B. subtilis enzyme does not promote any detectable cleavage of the E. coli bacteriophage lambda repressor.
INTERMEDIATES IN THE FOLDING REACTIONS OF SMALL PROTEINS (1990)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Why So Many Coinhibitory Receptors? (1999)

Receptors that display negative signalling functions on lymphocytes and other cells of the reticuloendothelial system now number about 30. These negative receptors are transmembrane glycoproteins activated by phosphorylation of a tyrosine residue in immunoreceptor tyrosine‐based inhibitory motifs that bind various phosphatases to induce dominant negative signals. Since these receptors are armed by the action of activating receptors and inhibit signalling by activating receptors, we have termed them coinhibitory receptors and the negative outcome is coinhibition. Coinhibitory receptors and some inhibitory mediators include FcγRIIB, CTLA‐4, CD5, CD22, p58/70/140 KIR, gp49B1/gp91, PIRB1‐5, LAIR‐1, NKB1, Ly49 A/C/E/F/G, NKG2‐A/B APC‐R, CD66, CD72, PD‐1, SHPS‐1, SIRP‐α1, ILT1‐5, MIR7,10, hMIR(HM18), hMIR(HM9), LIR1‐3,5,8, Fas (CD95), TGFβ‐R, TNF‐R1, IFNγ‐R (α and β chains), mast cell function Ag, H2‐M, HLA‐DM, CD1, CD1‐d, CD46, c‐cbl, Pyk2/FADK2, P130 Ca rel prot, PGDF‐R, LIF, LIF‐R, CIS, SOCS13 and 5, and others are being defined regularly. This long list suggests that coinhibitors are needed not only for self–nonself discrimination, but also for control of ongoing responses to foreign antigens so that infectious agents are ideally dealt with by an appropriate level of immune responses to nonself and an appropriate amount of immunopathology and sickness behaviour.
Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses (2001)

Gaucher disease is a typical lysosomal storage disease, resulting from an inborn deficiency of glucocerebrosidase. This leads to the accumulation of glycolipids in macrophages, particularly those in the liver, bone marrow, spleen and lung. In addition, disease of the nervous system can arise as a result of the accumulation of endogenous glycosphingolipid metabolites in brain tissue. About 150 mutations of the glucocerebrosidase gene have been identified in patients with Gaucher disease, some of which are predictive of phenotype. However, even patients and siblings with the same mutation, including monozygotic twins, may exhibit marked variability in disease expression and severity, illustrating our lack of understanding of the phenotype-genotype relationship in the sphingolipidoses. Massive organomegaly, particularly of the spleen, is a frequent feature of the disease. Although the liver and spleen may increase greatly in size, the amount of pathological lipid stored in the affected macrophages (Gaucher cells) accounts for less than 2% of the additional tissue mass. It is therefore clear that an inflammatory response occurs in affected individuals and that the clinical phenotype is due to an effect of macrophage storage beyond the physical presence of the Gaucher cells. Factors released by Gaucher cells, including pro-inflammatory cytokines and perhaps cathepsins, provide a mechanistic link between lysosomal storage and the diverse clinical manifestations of Gaucher disease. Emerging proteomic technology and gene expression profiling should not only improve our understanding of pathogenesis but also offer the prospect of identifying novel biomarkers that can be used as surrogate measures of disease activity and responses to treatment.
Application of Long Short-Term Memory (LSTM) Neural Network for Flood Forecasting (2019)

Flood forecasting is an essential requirement in integrated water resource management. This paper suggests a Long Short-Term Memory (LSTM) neural network model for flood forecasting, where the daily discharge and rainfall were used as input data. Moreover, characteristics of the data sets which may influence the model performance were also of interest. As a result, the Da River basin in Vietnam was chosen and two different combinations of input data sets from before 1985 (when the Hoa Binh dam was built) were used for one-day, two-day, and three-day flowrate forecasting ahead at Hoa Binh Station. The predictive ability of the model is quite impressive: The Nash–Sutcliffe efficiency (NSE) reached 99%, 95%, and 87% corresponding to three forecasting cases, respectively. The findings of this study suggest a viable option for flood forecasting on the Da River in Vietnam, where the river basin stretches between many countries and downstream flows (Vietnam) may fluctuate suddenly due to flood discharge from upstream hydroelectric reservoirs.
Porosity-Aware Buffered Steiner Tree Construction (2004)

In order to achieve timing closure on increasingly complex IC designs, buffer insertion needs to be performed on thousands of nets within an integrated physical synthesis system. Modern designs may contain large blocks which severely constrain the buffer locations. Even when there may appear to be space for buffers in the alleys between large blocks, these regions are often densely packed or may be needed later to fix critical paths. Therefore, within physical synthesis, a buffer insertion scheme needs to be aware of the porosity of the existing layout to be able to decide when to insert buffers in dense regions to achieve critical performance improvement and when to utilize the sparser regions of the chip. This work addresses the problem of finding porosity-aware buffering solutions by constructing a "smart Steiner tree" to pass to van Ginneken's topology-based algorithm. This flow allows one to fully integrate the algorithm into a physical synthesis system without paying an exorbitant runtime penalty. We show that significant improvements on timing closure are obtained when this approach is integrated into a physical synthesis system.
Optical Surface Transformation: Changing the optical surface by homogeneous optic-null medium at will (2015)

A new theory on designing electromagnetic/optical devices is proposed, namely, an optical surface transformation (OST). One arbitrary surface can establish the corresponding relationship with another surface entirely optically with an optic-null medium (ONM), (i.e. the electromagnetic wave propagates from one surface to its equivalent surface without any phase delay). Many novel optical devices can be designed by an OST with the help of an ONM. Compared with traditional devices designed by Transformation Optics, our optical surface-reshaping devices have two main advantages. Firstly, the design process is very simple (i.e. we do not need to consider any mathematics on how to make a coordinate transformation, and what we need to do is simply to design the shapes of the input and the output surfaces of the devices). Secondly, we only need one homogeneous anisotropic medium to realize all devices designed by this method. Our method will explore a new way to design novel optical devices without considering any coordinate transformations.
Identification of Sequences in the Herpes Simplex Virus Thymidine Kinase Gene Required for Efficient Processing and Polyadenylation (1985)

The herpes simplex virus (HSV) type 1 thymidine kinase gene (tk) was resected from its 3' end with BAL 31 exonuclease. Two sets of plasmids were isolated that lacked information distal to the two copies of the hexanucleotide 5'-AATAAA-3' located at the 3' end of the HSV tk gene. The presence of a simian virus 40 origin of DNA replication in each plasmid facilitated analysis of patterns of transcription in transfected Cos-1 monkey cells. Transcription analyses were performed with an S1 nuclease protection assay. Efficient processing and polyadenylation at the normal site still occurred when all sequences more than 44 or 46 base pairs (bp) downstream from the first AATAAA were removed (pTK311R/SV010 and pTK209R/SV010). Removal of an additional 7 bp (pTK312R/SV010) decreased the amount of tk mRNA processed at that normal site, and tk mRNA polyadenylated at a cryptic site within pBR322 sequences began to appear. The normal processing and polyadenylation site was not used at all when an additional 12 bp was removed (pTK314R/SV010); the small amount of tk mRNA produced was processed and polyadenylated at the cryptic pBR322 site. The region of the tk gene critical for efficient processing and polyadenylation of tk mRNA is located 20 to 38 bp downstream from the first AATAAA, distal to the polyadenylation site, and as RNA can form a stem-loop structure containing AAUAAA. Similar G + T-rich elements were located in DNA fragments which substitute efficiently for the HSV tk processing and polyadenylation signal and were not found in AATAAA-containing DNA fragments which substitute inefficiently for the HSV tk signal.
Dual targeting strategies with bispecific antibodies (2012)

Monoclonal antibodies are widely used for the treatment of cancer, inflammatory and infectious diseases and other disorders. Most of the marketed antibodies are monospecific and therefore capable of interacting and interfering with a single target. However, complex diseases are often multifactorial in nature, and involve redundant or synergistic action of disease mediators or upregulation of different receptors, including crosstalk between their signaling networks. Consequently, blockade of multiple, different pathological factors and pathways may result in improved therapeutic efficacy. This result can be achieved by combining different drugs, or use of the dual targeting strategies applying bispecific antibodies that have emerged as an alternative to combination therapy. This review discusses the various dual targeting strategies for which bispecific antibodies have been developed and provides an overview of the established bispecific antibody formats.