gebhart/patrepeval huggingface dataset:
Structural analysis, identification, and design of calcium‐binding sites in proteins (2002)

Assigning proteins with functions based on the 3-D structure requires high-speed techniques to make a systematic survey of protein structures. Calcium regulates many biological systems by binding numerous proteins in different biological environments. Despite the great diversity in the composition of ligand residues and bond angles and lengths of calcium-binding sites, our structural analysis of 11 calcium-binding sites in different classes of proteins has shown that common local structural parameters can be used to identify and design calcium-binding proteins. Natural calcium-binding sites in both EF-hand proteins and non-EF-hand proteins can be described with the smallest deviation from the geometry of an ideal pentagonal bipyramid. Further, two different magnesium-binding sites in parvalbumin and calbindin(D9K) can also be identified using an octahedral geometry. Using the established method, we have designed de novo calcium-binding sites into the scaffold of non-calcium-binding proteins CD2 and Rop. Our results suggest that it is possible to identify calcium- and magnesium-binding sites in proteins and design de novo metal-binding sites.
Myasthenia gravis with MuSK antibodies (2005)

<b>INTRODUCTION</b> Antibodies to the muscle acetylcholine receptor (AChR) are present in about 85% of patients with generalized myasthenia gravis, and 50% of patients with just ocular symptoms. However, up to 70% of the myasthenia patients without AChR antbodies, so called ‘seronegative’ myasthenia gravis, have antibodies to the muscle specific tyrosine kinase (MuSK). MuSK is another protein at the postsynaptic membrane of the neuromuscular junction, and plays a role in agrin-induced AChR clustering (Hoch <i>et al</i>. 2001). These patients may be difficult to recognize, and difficult to treat effectively. Here we describe four AChR antibody-negative/MuSK antibody-positive patients as examples. <b>THE CASES (SEE TABLE 1)</b> <b>Case 1</b> This patient had an age at onset and clinical presentation typical of myasthenia gravis but was difficult to treat. She was a 30-year old woman who developed diplopia, dysphagia and dysarthria during the third trimester of her first pregnancy. EMG showed a defect of neuromuscular
Closing the Gap Between Research and Field Applications for Multi-UAV Cooperative Missions (2013)

The ability to fly multiple unmanned aerial vehicles (UAVs) in collaboration has the potential to expand the scope of feasible UAV missions and could become the backbone of future UAV missions. However, despite having garnered significant research interest, there is no indication that systems supporting collaborative operation of multiple UAVs are close to achieving field deployment. The challenge of successfully deploying a quality system is inherently complex, and systems engineering offers an approach to handle the complexities. Effective application of systems engineering requires both knowledge breadth and depth. This thesis presents the results of a consolidation of information intended to support the conduct of systems engineering activities; and describes an experiment to ascertain the sensitivities of some key operational parameters, e.g., acquisition, pointing, and tracking. The experiment was conducted using Automatic Dependent SurveillanceBroadcast (ADS-B) and visual tracking equipment employing state-of-the-art technology to understand the operating challenges and requirements of using this equipment to provide situational awareness for a UAV pilot.
FRACTIONATED RADIOIMMUNOTHERAPY OF HUMAN COLON CARCINOMA XENOGRAFTS WITH 131I-CC49 MONOCLONAL ANTIBODY (1994)

s: Fifth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer: Session VI: Experimental Radioimmunotherapy: PDF Only
Carboplatin induces Fas (APO‐1/CD95)‐dependent apoptosis of human tongue carcinoma cells: Sensitization for apoptosis by upregulation of FADD expression (2003)

We examined the apoptosis of tongue carcinoma cells and the effects of anticancer drugs to identify the molecules that mediate apoptotic cascade in the malignancy. Carboplatin (CBDCA) induced apoptosis of SCC-9 and SCC-25, human well-differentiated tongue squamous carcinoma cell lines. Neutralizing anti-Fas (APO-1/CD95) and anti-Fas ligand (FasL) antibodies obliterated the CBDCA-induced cell death. In the absence of CBDCA, cytotoxic anti-Fas antibody, which binds to and activates Fas at the cell surface, failed to induce apoptosis. However, in the presence of CBDCA, the cytotoxic antibody markedly enhanced the apoptosis in a dose-dependent manner. Western blotting and reverse-transcription (RT) PCR revealed that there were no alterations in Fas or FasL expression upon CBDCA treatment. SCC-25 induced apoptosis of Jurkat cells, Fas-sensitive T-lymphatic leukemia cell line, and the apoptosis was inhibited by neutralizing anti-Fas or anti-FasL antibody. These results indicate that the tongue carcinoma cells express nonfunctional Fas and functional FasL, which by themselves fail to induce apoptosis. The expression of FADD in the tongue carcinoma cells was very low and was largely enhanced by CBDCA treatment. Suppression of FADD expression using the specific antisense oligonucleotide resulted in a failure of CBDCA induction of cell death. These results indicate that a deficiency of FADD is involved in the insensitivity of tongue carcinoma cells for Fas activation, and that CBDCA treatment switches nonfunctional Fas to functional Fas by upregulation of FADD expression, resulting in activation of a Fas-sensitive pathway leading to apoptosis.
AS1411-conjugated gold nanospheres and their potential for breast cancer therapy (2015)

AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein present on the surface of cancer cells. Clinical trials of AS1411 have indicated it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. In this report, we describe how conjugating AS1411 to 5 nm gold nanospheres influences its activities in vitro and in vivo. We find that the AS1411-linked gold nanospheres (AS1411-GNS) are stable in aqueous and serum-containing solutions. Compared to unconjugated AS1411 or GNS linked to control oligonucleotides, AS1411-GNS have superior cellular uptake and markedly increased antiproliferative/cytotoxic effects. Similar to AS1411, AS1411-GNS show selectivity for cancer cells compared to non-malignant cells. In a mouse model of breast cancer, systemic administration of AS1411-GNS could completely inhibit tumor growth with no signs of toxicity. These results suggest AS1411-GNS are promising candidates for clinical translation.
Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis (2009)

To determine the cytokine balance in patients with lupus nephritis (LN), we analysed kidney-infiltrating T cells. Renal biopsy samples from 15 systemic lupus erythematosus (SLE) patients were used. In accordance with the classification of International Society of Nephrology/Renal Pathology Society, they were categorized into Class III, Class III+V (Class III-predominant group, n = 4), Class IV, Class IV+V (Class IV-predominant group, n = 7) and Class V (n = 4) groups. The single-cell samples of both the glomelular and interstitial infiltrating cells were captured by laser-microdissection. The glomerular and interstitial infiltrating T cells produced interleukin (IL)-2, IL-4, IL-10, IL-13 and IL-17 cytokines in the Class III-predominant, Class IV-predominant and Class V groups. Interferon-gamma was detected only in the glomeruli of the Class III-predominant and Class V group samples. The expression level of IL-17 was correlated closely with clinical parameters such as haematuria, blood urea nitrogen level, SLE Disease Activity Index scores in both glomeruli and interstitium, urine protein level in glomeruli and serum creatinine and creatinine clearance levels in interstitium. This suggests that the glomerular infiltrating T cells might act as T helper type 1 (Th1), Th2 and Th17 cells while the interstitial infiltrating T cells, act as Th2 and Th17 cells in the Class III-predominant and Class V groups. In contrast, both the glomerular and interstitial infiltrating T cells might act as Th2 and Th17 cells in the Class IV-predominant group. The cytokine balances may be dependent upon the classification of renal pathology, and IL-17 might play a critical role in SLE development.
Induction of Apoptosis in Leukemic Cells by Homovanillic Acid Derivative, Capsaicin, through Oxidative Stress (2004)

Capsaicin (N-vanillyl-8-methyl-1-nonenamide) is a homovanillic acid derivative found in pungent fruits. Several investigators have reported the ability of capsaicin to inhibit events associated with the promotion of cancer. However, the effects of capsaicin on human leukemic cells have never been investigated. We investigated the effects of capsaicin on leukemic cells in vitro and in vivo and further examined the molecular mechanisms of capsaicin-induced apoptosis in myeloid leukemic cells. Capsaicin suppressed the growth of leukemic cells, but not normal bone marrow mononuclear cells, via induction of G(0)-G(1) phase cell cycle arrest and apoptosis. Capsaicin-induced apoptosis was in association with the elevation of intracellular reactive oxygen species production. Interestingly, capsaicin-sensitive leukemic cells were possessed of wild-type p53, resulting in the phosphorylation of p53 at the Ser-15 residue by the treatment of capsaicin. Abrogation of p53 expression by the antisense oligonucleotides significantly attenuated capsaicin-induced cell cycle arrest and apoptosis. Pretreatment with the antioxidant N-acetyl-L-cystein and catalase, but not superoxide dismutase, completely inhibited capsaicin-induced apoptosis by inhibiting phosphorylation of Ser-15 residue of p53. Moreover, capsaicin effectively inhibited tumor growth and induced apoptosis in vivo using NOD/SCID mice with no toxic effects. We conclude that capsaicin has potential as a novel therapeutic agent for the treatment of leukemia.
Blood culture technique based on centrifugation: developmental phase (1976)

A quantitative and flexible blood culture system based on centrifugation of lysed blood over a density layer is described. The effect of relative centrifugal force, centrifugation time, and two different density solutions on the recovery of Staphylococcus aureus, Escherichia coli, pseudomonas aeruginosa, and Candida albicans was determined. To demonstrate the versatility of this technique, the reisolation of 23 representative microorganisms from inoculated normal human blood was determined at a fixed centrifugation speed and time. The potential merits of this technique are discussed and compared with those of conventional blood culture methods.
Complement Activation by Direct C4 Binding to Thyroperoxidase in Hashimoto’s Thyroiditis (2003)

Biosynthesis of thyroid hormones is an oxidative process that generates reactive oxygen species (ROS) and involves thyroperoxidase (TPO) that is one of the main autoantigens involved in autoimmune thyroid diseases. The ectodomain of TPO consists of a large N-terminal myeloperoxidase-like module followed by a complement control protein (CCP)-like module and an epidermal growth factor-like module. The presence of these two additional gene modules suggests that they may play some crucial, hitherto unsuspected role associated with thyroid function. Because the CCP module is a constituent of the molecules involved in the activation of C4 complement component, we investigated the possibility that C4 may bind to TPO and activate the complement pathway in autoimmune conditions. We showed that TPO via its CCP module directly activated complement without any mediation by Ig. We suggested that this additional complement pathway requires the production of ROS and specially hydroxyl radicals that aggregate TPO and oxidize methionines of C4. Moreover, we found, in patients with Hashimoto's thyroiditis, that thyrocytes overexpress C4 and all the downstream components of the complement pathway. These results indicate that TPO has some as yet unknown function, which may contribute along with other mechanisms to the massive cell destruction observed in Hashimoto's thyroiditis. Investigating this complement pathway, therefore, would provide an excellent means of reaching a better understanding of the etiology of other degenerative diseases.
Recombinant, Live-Attenuated Tetravalent Dengue Virus Vaccine Formulations Induce a Balanced, Broad, and Protective Neutralizing Antibody Response against Each of the Four Serotypes in Rhesus Monkeys (2005)

Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-wt) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant DEN1, -2, -3, and -4, each with a 30-nucleotide deletion in the 3' untranslated region (Delta30). TV-2 consists of rDEN1Delta30, rDEN4Delta30, and two antigenic chimeric viruses, rDEN2/4Delta30 and rDEN3/4Delta30, both also bearing the Delta30 mutation. TV-3 consists of rDEN1Delta30, rDEN2Delta30, rDEN4Delta30, and a 10-fold higher dose of rDEN3/4Delta30. TV-1 and TV-2 were attenuated in SCID-HuH-7 mice with minimal interference in replication among the virus components. TV-1, -2, and -3 were attenuated in rhesus monkeys as measured by duration and peak of viremia. Each monkey immunized with TV-1 and TV-3 seroconverted to the four DEN components by day 28 with neutralization titers ranging from 1:52 to 1:273 and 1:59 to 1:144 for TV-1 and TV-3, respectively. TV-2 induced low antibody titers to DEN2 and DEN3, but a booster immunization after 4 months increased the neutralizing antibody titers to greater than 1:100 against each serotype and elicited broad neutralizing activity against 19 of 20 DEN subtypes. A single dose of TV-2 induced protection against wild-type DEN1, DEN3, and DEN4 challenge, but not DEN2. However, two doses of TV-2 or TV-3 induced protection against DEN2 challenge. Two tetravalent formulations, TV-2 and TV-3, possess properties of a successful DEN vaccine and can be considered for evaluation in clinical trials.
Nonlinear benchmark system identification with partial states measurement (2003)

We propose a novel identification algorithm for a nonlinear benchmark problem: rotational-translational actuator. The conventional identification is modified in two ways: (1) a model-free nonlinear observer is applied to get the whole states; (2) the dynamic multilayer neural network is used to identify the nonlinear system.
Equine arteritis virus is not a togavirus but belongs to the coronaviruslike superfamily (1991)

The nucleotide sequence of the genome of equine arteritis virus (EAV) was determined from a set of overlapping cDNA clones and was found to contain eight open reading frames (ORFs). ORFs 2 through 7 are expressed from six 3'-coterminal subgenomic mRNAs, which are transcribed from the 3'-terminal quarter of the viral genome. A number of these ORFs are predicted to encode structural EAV proteins. The organization and expression of the 3' part of the EAV genome are remarkably similar to those of coronaviruses and toroviruses. The 5'-terminal three-quarters of the genome contain the putative EAV polymerase gene, which also shares a number of features with the corresponding gene of corona- and toroviruses. The gene contains two large ORFs, ORF1a and ORF1b, with an overlap region of 19 nucleotides. The presence of a "shifty" heptanucleotide sequence in this region and a downstream RNA pseudoknot structure indicate that ORF1b is probably expressed by ribosomal frameshifting. The frameshift-directing potential of the ORF1a/ORF1b overlap region was demonstrated by using a reporter gene. Moreover, the predicted ORF1b product was found to contain four domains which have been identified in the same relative positions in coronavirus and torovirus ORF1b products. The sequences of the EAV and coronavirus ORF1a proteins were found to be much more diverged. The EAV ORF1a product contains a putative trypsinlike serine protease motif. Our data indicate that EAV, presently considered a togavirus, is evolutionarily related to viruses from the coronaviruslike superfamily.
Aspergillus oryzae laeARegulates Kojic Acid Synthesis Genes (2011)

Kojic acid synthesis genes regulation was investigated in Aspergillus oryzae. Our results indicate that kojic acid production was lost in the laeA disruption strain, but was recovered in the LaeA complement strain. Real-time PCR also confirmed that expression of kojic acid biosynthesis genes decreased in the laeA disruption strain, indicating that these genes are under the control of LaeA.
Divergent envelope E2 alphavirus sequences spanning amino acids 297 to 352 induce in mice virus-specific protective immunity and antibodies with complement-mediated cytolytic activity (1992)

We have proposed a general algorithm for identification of potential immunoprotective domains (cassettes) on the envelope E2 polypeptide of alphaviruses (H. Grosfeld, B. Velan, M. Leitner, S. Cohen, S. Lustig, B.E. Lachmi, and A. Shafferman, J. Virol. 63:3416-3422, 1989). To assess the generality of our approach, we compared analogous E2 cassettes from Sindbis virus (SIN) and Semliki Forest virus (SFV), two alphaviruses which are philogenetically very remote. The antigenically distinct SFV E2 and SIN E2 cassettes exhibit comparable immunological characteristics. Most significantly, the SIN E2 LMN cassette cluster (E2 amino acids 297 to 352 fused to beta-galactosidase), like the analogous SFV E2 LMN cassettes, elicited high titers of antivirus antibodies in mice and proved to be highly effective in protection against lethal challenge. Mice immunized with SIN E2 LMN were completely protected against intracerebral challenge of 10 to 100 50% lethal doses of different neurovirulent SIN strains. Anti-SIN LMN antibodies, like anti-SFV LMN antibodies, lacked in vitro neutralizing activity, yet both exerted protection against homologous challenge upon transfer to mice. The two antibody preparations exhibited virus-specific complement-mediated cytolysis of cells infected with the homologous but not heterologous virus. These results suggest a possible mechanism for virus-specific E2 LMN-induced protection and demonstrate the generality of our methodology for deciphering immunogenic and protective domains in alphavirus systems. Results suggest also that the E2 LMN sequence of any given alphavirus should be considered as a component of a synthetic vaccine against that specific virus.
Sensitivity of laser opto-acoustic imaging in detection of small deeply embedded tumors (1999)

Current imaging modalities fail to detect small tumors in the breast. Opto-acoustic tomography is a novel technique for early cancer detection with promising diagnostic capability. The experimental limit of sensitivity and maximal depth of the laser opto-acoustic detection for small model tumors located within bulk phantom tissue were studied. Two phantoms with optical properties similar to that of breast tissue in the near infrared spectral range were used in these studies: turbid gelatin slabs with the thickness of 100 mm and chicken breast muscle slabs with the thickness of up to 80 mm. Gelatin spheres with enhanced absorption coefficient relative to the background absorption and liver tissue were used to simulate small tumors. The experiments demonstrated the capability of laser optoacoustic imaging to detect and localize phantom tumors with the diameter of 2 mm at a depth of up to 60 mm within the gelatin phantoms and 3/spl times/2/spl times/0.6-mm piece of liver tissue within 80-mm chicken breast tissue. Theoretical studies on sensitivity of opto-acoustic detection at various diameters, depths of location, and absorption coefficients of small tumors were performed using the experimental data. Our results suggest that the opto-acoustic imaging may occupy a significant niche in early detection of cancer in the breast and other organs.
The Role of Glycogen Synthase Kinase 3-β in Immunity and Cell Cycle: Implications in Esophageal Cancer (2013)

Esophageal cancer (EC) is one of the most aggressive gastrointestinal malignancies, possessing an insidious onset and a poor prognosis. Numerous transcription factors and inflammatory mediators have been reported to play a pivotal role in the initiation and progression of this cancer. However, the specifics of the signaling network responsible for said factors, especially which elements are the critical regulators, are still being elucidated. Glycogen synthesis kinases 3 (GSK3)β was originally regarded as a kinase regulating glucose metabolism. Accumulating evidence demonstrated that it also played an essential role in a variety of cellular processes including proliferation, differentiation, inflammation, motility, and survival by regulating various transcription factors such as c-Jun, AP-1, β-catenin, CREB, and NF-κB. Aberrant regulation of GSK3β has been shown to promote cell growth in some cancers, while suppressing it in others, and thus may play an important role in the development of EC. This review will discuss our current understanding of GSK3β signaling, and its control of the expression and activation of various transcription factors that mediate the inflammatory response. We will also explore some of the known mediators of EC progression, and based on current literature, elucidate the potential roles and implications of GSK3 in this disease.
Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer (2005)

Hemophilia A is a clinically important coagulation disorder caused by the lack or abnormality of plasma coagulation factor VIII (FVIII). Gene transfer of the FVIII cDNA to hepatocytes using lentiviral vectors is a potential therapeutic approach. We investigated the efficacy of feline immunodeficiency virus (FIV)-based vectors in targeting hepatocytes and correcting FVIII deficiency in a hemophilia A mouse model. Several viral envelope glycoproteins were screened for efficient FIV vector pseudotyping and hepatocyte transduction. The GP64 glycoprotein from baculovirus Autographa californica multinuclear polyhedrosis virus pseudo-typed FIV efficiently and showed excellent hepatocyte tropism. The GP64-pseudotyped vector was stable in the presence of human or mouse complement. Inclusion of a hybrid liver-specific promoter (murine albumin enhancer/human alpha1-antitrypsin promoter) further enhanced transgene expression in hepatocytes. We generated a GP64-pseudotyped FIV vector encoding the B domain-deleted human FVIII coding region driven by the liver-specific promoter, with 2 beneficial point mutations in the A1 domain. Intravenous vector administration conferred sustained FVIII expression in hemophilia A mice for several months without the generation of anti-human FVIII antibodies and resulted in partial phenotypic correction. These findings demonstrate the utility of GP64-pseudotyped FIV lentiviral vectors for targeting hepatocytes to correct disorders associated with deficiencies of secreted proteins.