gebhart/patrepeval huggingface dataset:
Correlated mutations and residue contacts in proteins (1994)

The maintenance of protein function and structure constrains the evolution of amino acid sequences. This fact can be exploited to interpret correlated mutations observed in a sequence family as an indication of probable physical contact in three dimensions. Here we present a simple and general method to analyze correlations in mutational behavior between different positions in a multiple sequence alignment. We then use these correlations to predict contact maps for each of 11 protein families and compare the result with the contacts determined by crystallography. For the most strongly correlated residue pairs predicted to be in contact, the prediction accuracy ranges from 37 to 68% and the improvement ratio relative to a random prediction from 1.4 to 5.1. Predicted contact maps can be used as input for the calculation of protein tertiary structure, either from sequence information alone or in combination with experimental information.
NetKuang: a multi-host configuration vulnerability checker (1996)

NetKuang is an extension to Baldwin&amp;apos;s SU-Kuang. It runs on networks of computers using Unix and can find vulnerabilities created by poor system configuration. Vulnerabilities are discovered using a backwards goal-based search that is breadth-first on individual hosts and parallel when multiple hosts are checked. An implementation in C++ found real vulnerabilities on production systems. Tests show reasonably fast performance on an LAN. 1 Introduction The security of modern networked computer systems is dependent on more than just the integrity of the software and protection mechanisms their operating systems use; it is also dependent on the proper configuration and use of that software. Unix computers have a wide variety of security mechanisms such as file permissions, passwords, trusted hosts, and so forth. In practice, such mechanisms can quickly grow very complex. A simple configuration error can lead to users gaining unintended access. The problem has grown worse with the popularit...
Changing the Antigen Binding Specificity by Single Point Mutations of an Anti-p24 (HIV-1) Antibody (2000)

The murine mAb CB4-1 raised against p24 (HIV-1) recognizes a linear epitope of the HIV-1 capsid protein. Additionally, CB4-1 exhibits cross-reactive binding to epitope-homologous peptides and polyspecific reactions to epitope nonhomologous peptides. Crystal structures demonstrate that the epitope peptide (e-pep) and the nonhomologous peptides adopt different conformations within the binding region of CB4-1. Site-directed mutagenesis of the fragment variable (Fv) region was performed using a single-chain (sc)Fv construct of CB4-1 to analyze binding contributions of single amino acid side chains toward the e-pep and toward one epitope nonhomologous peptide. The mutations of Ab amino acid side chains, which are in direct contact with the Ag, show opposite influences on the binding of the two peptides. Whereas the affinity of the e-pep to the CB4-1 scFv mutant heavy chain variable region Tyr(32)Ala is decreased 250-fold, the binding of the nonhomologous peptide remains unchanged. In contrast, the mutation light chain variable region Phe(94)Ala reduces the affinity of the nonhomologous peptide 10-fold more than it does for the e-pep. Thus, substantial changes in the specificity can be observed by single amino acid exchanges. Further characterization of the scFv mutants by substitutional analysis of the peptides demonstrates that the effect of a mutation is not restricted to contact residues. This method also reveals an inverse compensatory amino acid exchange for the nonhomologous peptide which increases the affinity to the scFv mutant light chain variable region Phe(94)Ala up to the level of the e-pep affinity to the wild-type scFv.
Irradiation System for HIMAC (2007)

Clinical trials of carbon radiotherapy started at HIMAC in 1994 using three treatment rooms and four beam ports, two horizontal and two vertical. The broad beam method was adopted to make a three-dimensionally uniform field at an isocenter. A spot beam extracted from an accelerator was laterally spread out by using a pair of wobbler magnets and a scatterer. A bar ridge filter modulated the beam energy to obtain the spread out Bragg peak (SOBP). The SOBP was designed to be flat in terms of the biological dose based on the consideration that the field consisted of various beams with different LET. Finally, the field of 20 cm in diameter with +/- 2.5% uniformity was formed at the isocenter. The width of the maximum SOBP was 15 cm. When treating the lung or liver, organs that move due to breathing, the beam was irradiated only during the expiration period in a respiration-gated irradiation method. This reduced the treatment margin of the moving target. In order to prevent normal tissues adjacent to the target volume from irradiation by an unwanted dose, a layer-stacking method was developed. In this method, thin SOBP layers which have different ranges were piled up step by step from the distal end to the entrance of the target volume. At the same time, a multi-leaf collimator was used to change the aperture shape to match the shape of each layer to the cross-sectional shape of the target. This method has been applied to rather large volume cancers including bone and soft-tissue cancers. Only a few serious problems in the irradiation systems have been encountered since the beginning of the clinical trials. Overall the systems have been working stably and reliably.
Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. (1984)

Cholera toxin (CT) has been found to be an extremely potent immunogen for mucosal IgA responses when administered via the intestine. This study has examined both mucosal and systemic immune responses after feeding CT and compared these responses with those obtained after feeding keyhole limpet hemocyanin (KLH), another protein that is strongly immunogenic in mice. Feeding CT to mice resulted not only in IgA antibody in intestinal secretions but also resulted in substantial plasma IgG and IgA antibody levels. Feeding KLH in much larger quantity resulted in little or no antibody response in intestinal secretions or plasma. Lymphoid cells from various tissues of mice fed CT were cultured in vitro for 10 days and the supernatant was tested for antibody to CT. Spontaneous antibody synthesis (no antigen added to cultures) was present in cultures of each cell type, but IgG anti-CT was found mainly in cultures of spleen and mesenteric lymph node cells and IgA anti-CT mainly in cultures of Peyer's patch and lamina propria cells. Peyer's patch cells cultured with CT as antigen synthesized both IgG and IgA anti-CT, suggesting that the antibody response to both isotypes originated in this site. Helper T cell activity for both IgA and IgG anti-CT was detected in spleens, mesenteric lymph nodes, and Peyer's patches. Lastly, when KLH and CT were fed to mice at the same time, an intestinal IgA anti-KLH and plasma IgG anti-KLH response was stimulated, a response pattern similar to that occurring to CT after CT was fed alone. We conclude that mucosal stimulation by CT generates both a systemic IgG and mucosal IgA response to this antigen, and that CT can cause a similar pattern of response to an unrelated protein antigen when both are administered into the intestine at the same time. The data favor the idea that both the IgG and IgA responses originate in GALT and then disseminate to other tissues. We propose that CT accomplishes these effects by altering the regulatory environment within GALT.
Growth of aligned carbon nanotubes by plasma-enhanced chemical vapor deposition: Optimization of growth parameters (2001)

Direct-current plasma-enhanced chemical vapor deposition (CVD) with mixtures of acetylene and ammonia was optimized to synthesize aligned carbon nanotubes (CNTs) on Co- or Ni-covered W wires with regard to wire temperature, wire diameter, gas pressure, and sample bias. A phase diagram of CNT growth was established experimentally in this optimization process. It was revealed by transmission electron microscopy that Co-catalyzed CNTs encapsulated a Co carbide nanoparticle at their tip, disagreeing with a previous report that Co particles were located at the base of CNTs CVD grown on Co-covered Si substrates [C. Bower et al., Appl. Phys. Lett. 77, 2767 (2000)]. This leads to the conclusion that the formation mechanism of aligned CNTs depends significantly on the catalyst support material as well as the catalyst material itself. Since the sample bias strongly affected the morphology of CNTs, the selective supply of positive ions to CNT tips was possibly responsible for the alignment of growing CNTs.
Isolation and characterization of cDNA clones for the mouse thymocyte B cell antigen (ThB) (1992)

The Thb locus is responsible for the expression of 15-kDa phosphatidyl inositol anchored molecules (ThB) on murine thymocytes and B cells. Thb expression as detected with mAb is polymorphic on B cells with two alleles, Thbh and Thb1 responsible for the high and low expression of ThB on B cells. The regulatory locus for Thb expression had been mapped with the Ly-6 cluster of genes to Chr 15. In our study we used expression cloning in COS cells to isolate cDNA clones that code for ThB after transfection; the cDNA products react with anti- ThB antibodies, but not with Ly-6A.2, -6B.2, -6C.2, or -6D.2 antibodies. One of these clones, pThB-A contains insert of 702 bases which was sequenced. The translated amino acid sequence has 11 cysteine residues, and together with the absence of potential N-linked glycosylation sites is similar to the structure of the Ly-6 molecules. The nucleotide and amino acid sequences of ThB cDNA were compared to those of Ly-6 genes and the Ly-6 related human CD59 and show clear homology. Finally using interspecies crosses, the structural Thb gene has been mapped to Chr 15; thus both structural and regulatory genes map to a similar site. The genetic map location near Ly-6 and the sequence similarity suggest that Thb and Ly-6 may have been derived from the same progenitor by gene duplication.
Identification and analysis of a glutaryl‐CoA dehydrogenase‐encoding gene and its cognate transcriptional regulator from Azoarcus sp. CIB (2007)

Summary In this work, the gcdH gene from the denitrifying β‐proteobacterium Azoarcus sp. CIB was shown to encode a glutaryl‐CoA dehydrogenase, which is essential for the anaerobic catabolism of many aromatic compounds and some alicyclic and dicarboxylic acids. The primary structure of the GcdH protein is highly conserved in many organisms. The divergently transcribed gcdR gene, encoding a LysR‐type transcriptional regulator, accounts for the glutaconate/glutarate‐specific activation of the Pg promoter driving expression of gcdH . The Azoarcus sp. CIBd gcdH mutant strain harbouring a disrupted gcdH gene was used as host to identify heterologous gcdH genes, such as that from Pseudomonas putida KT2440. Moreover, the expression of gcdH from P. putida can be efficiently controlled by the GcdR activator in Azoarcus sp. CIB, demonstrating the existence of cross‐talk between GcdR regulators and gcdH promoters from members of different phylogenetic subgroups of proteobacteria.
Anisotropic Chemical Reactivity of Gold Spheroids and Nanorods (2002)

We observed anisotropic chemical reactivity of gold spheroids during cyanide dissolution and reaction with persulfate. Cyanide dissolution of 2−5 aspect ratio spheroids (with 12−30 nm short axis) starts at the ends of the long axis and leads to intermediate lower aspect ratio spheroids and spheres. Persulfate converts the spheroids into spheres. In contrast, cyanide dissolution of 18 aspect ratio nanorods (with 16 nm short axis) starts simultaneously at many sites and does not change the nanorod length throughout dissolution. Spheroids are thermally less stable than rods and slowly convert to spheres with time, and thus anisotropic chemical reactivity is presumably due to their lower stability.
Editor's Comment (2003)

Theatre Topics is a unique journal in that it offers us the opportunity as theatre educators, scholars, and practitioners to reflect not only on what we do, but also on how we do it—how we teach, how we do our research, how we write, how we perform. Most Theatre Topics essays have a kind of meta-quality, a rich self-consciousness of process and purpose. I am delighted to introduce six essays for this issue of Theatre Topics that exemplify the range of the journal's subjects and styles. To me, all of these essays perform an intervention, whether historical, theoretical, pedagogical, or performative.
Preclinical evaluation of bryostatin as an anticancer agent against several murine tumor cell lines: in vitro versus in vivo activity. (1992)

We have examined the ability of bryostatin 1 to inhibit the in vitro growth and in vivo development of a panel of four murine tumors of diverse tissue origins. A wide range of antiproliferative responses was observed for the four tumors. At 100 ng/ml the in vitro growth of the Renca renal adenocarcinoma, the B16 melanoma, the M5076 reticulum cell sarcoma, and the L10A B-cell lymphoma were inhibited by 0, 40, 40, and 94% respectively. All three cell lines sensitive to bryostatin in vitro responded to multiple dose, 1 microgram/injection/day in vivo i.p., bryostatin therapy. Only the in vitro resistant Renca tumor failed to respond to bryostatin in vivo. The correlation between in vitro and in vivo antitumor efficacy suggests a direct mechanism of antitumor activity for bryostatin. Both local regional therapy (M5076 i.p.) and systemic therapy (B16 lung metastases and L10A s.c. tumors) with bryostatin were successful at prolonging survival time. Multiple i.p. doses of bryostatin at a minimum level of 0.5-1.0 microgram/injection were required to observe significant in vivo antitumor effects. The success of in vivo administration of bryostatin in mice bearing 8-10-mm s.c. masses of L10A lymphoma (5-10 x 10(9)) and our further observation that five of a panel of six human B-cell lymphoma cell lines were sensitive to the growth inhibitory effects of bryostatin in vitro suggest that bryostatin may be effective in treating lymphoid malignancies in humans.
Breast cancer classification and prognosis based on gene expression profiles from a population-based study (2003)

Comprehensive gene expression patterns generated from cDNA microarrays were correlated with detailed clinico-pathological characteristics and clinical outcome in an unselected group of 99 node-negative and node-positive breast cancer patients. Gene expression patterns were found to be strongly associated with estrogen receptor (ER) status and moderately associated with grade, but not associated with menopausal status, nodal status, or tumor size. Hierarchical cluster analysis segregated the tumors into two main groups based on their ER status, which correlated well with basal and luminal characteristics. Cox proportional hazards regression analysis identified 16 genes that were significantly associated with relapse-free survival at a stringent significance level of 0.001 to account for multiple comparisons. Of 231 genes previously reported by others [van't Veer, L. J., et al. (2002) Nature 415, 530-536] as being associated with survival, 93 probe elements overlapped with the set of 7,650 probe elements represented on the arrays used in this study. Hierarchical cluster analysis based on the set of 93 probe elements segregated our population into two distinct subgroups with different relapse-free survival (P < 0.03). The number of these 93 probe elements showing significant univariate association with relapse-free survival (P < 0.05) in the present study was 14, representing 11 unique genes. Genes involved in cell cycle, DNA replication, and chromosomal stability were consistently elevated in the various poor prognostic groups. In addition, glutathione S-transferase M3 emerged as an important survival marker in both studies. When taken together with other array studies, our results highlight the consistent biological and clinical associations with gene expression profiles.
Development of long life three phase uninterruptible power supply using flywheel energy storage unit (2002)

According to the development of computer applications, uninterruptible power supplies (UPS) are indispensable to the industrial field. But the cost of maintaining a conventional UPS is very high, because frequent replacement of parts which have short lifetime is necessary. This paper describes the research and development of a new UPS which has long life parts for maintenance free operation. To lengthen the lifetime, the following techniques are introduced: (1) a flywheel energy storage unit having more than 20 years lifetime; and (2) an electrolytic capacitorless inverter and power converter. By using these techniques, a three-phase UPS rated 5 kVA, 200 V is developed, and excellent performance is obtained: input power factor is over 99.7%; output voltage distortion is under 1.6%; the transformerless UPS produces a lightweight system; the UPSs have the function of automatic output voltage balance using auxiliary diode rectifier; and input current harmonic distortion is less than 1.2%, even if a single-phase load is connected.
Nitric oxide synthase is a cytochrome P-450 type hemoprotein (1992)

Nitric oxide has emerged as an important mammalian metabolic intermediate involved in critical physiological functions such as vasodilation, neuronal transmission, and cytostasis. Nitric oxide synthase (NOS) catalyzes the five-electron oxidation of L-arginine to citrulline and nitric oxide. Cosubstrates for the reaction include molecular oxygen and NADPH. In addition, there is a requirement for tetrahydrobiopterin. NOS also contains the coenzymes FAD and FMN and demonstrates significant amino acid sequence homology to NADPH-cytochrome P-450 reductase. Herein we report the identification of the inducible macrophage NOS as a cytochrome P-450 type hemoprotein. The pyridine hemochrome assay showed that the NOS contained a bound protoporphyrin IX heme. The reduced carbon monoxide binding spectrum shows an absorption maximum at 447 nm indicative of a cytochrome P-450 hemoprotein. A mixture of carbon monoxide and oxygen (80%/20%) potently inhibited the reaction (73-79%), showing that the heme functions directly in the oxidative conversion of L-arginine to nitric oxide and citrulline. Additionally, partially purified NOS from rat cerebellum was inhibited by CO, suggesting that this isoform may also contain a P-450-type heme. NOS is the first example of a soluble cytochrome P-450 in eukaryotes. In addition, the presence of FAD and FMN indicates that this is the first catalytically self-sufficient mammalian P-450 enzyme, containing both a reductase and a heme domain on the same polypeptide.
Phosphorylation of the amyloid precursor protein (APP): Is this a mechanism in favor or against Alzheimer's disease? (2004)

Abstract This review discusses the phosphorylation of the Amyloid Precursor Protein (APP) and the possible role of this phosphorylation in Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by the deposition of β‐amyloid plaques in the brain parenchyma and neurofibrillary tangles comprised of hyperphosphorylated tau. APP plays a primary role in the pathogenesis of AD, because its processing generates the amyloid beta peptide (Aβ), the core of the amyloid plaque. APP has a large N‐terminal extracellular domain and a short intracellular C‐terminal domain that can be phosphorylated by various protein kinases. This review summarized recent work describing the phsphorylation of APP and the downstream events induced by this phosphorylation as well as the impact of APP phosphorylation on APP function and on the production of Aβ peptide.
Predictive markers in breast cancer – the present (2007)

Breast cancer is a heterogeneous disease and there is a continual drive to identify markers that will aid in predicting prognosis and response to therapy. To date, relatively few markers have established prognostic power. Oestrogen receptor (ER) is probably the most powerful predictive marker in breast cancer management, both in determining prognosis and in predicting response to hormone therapies. Progesterone receptor (PR) is also a widely used marker, although its value is less well established. HER-2 status has also become a routine prognostic and predictive factor in breast cancer. Given the importance of these biological markers in patient management, it is essential that assays are robust and quality controlled, and that interpretation is standardized. Furthermore, it is important to be aware of the limitations in their predictive power, and how this may be refined through addition of further biological markers. The aim of this review is to provide an overview of the established role of ER, PR and HER-2 in patient management, the current standards for assessing these markers, as well as highlighting the controversies that still surround their use and methods of assessment.
Oligoarginine vectors for intracellular delivery: Design and cellular‐uptake mechanisms (2005)

Intracellular delivery using membrane-permeable peptide vectors is a recently developed methodology that has been employed successfully to transport various bioactive molecules into cells to modify cell functions. The efficient delivery of proteins, peptides, nucleic acids, liposomes, and so on has been accomplished using this methodology by conjugation of a peptide vector with the cargo molecules. The potentials of this approach for medical and pharmaceutical applications has also attracted our attention. Arginine-rich peptides, including a basic peptide segment derived from the human immunodeficiency virus type 1 (HIV-1) Tat protein, are categorized into one of the most frequently used peptide vectors, and the efforts of designing novel vectors have been ongoing. Internalization of these peptides has previously been regarded as not employing endocytosis. However, recent reevaluations have demonstrated the significant involvement of endocytosis in the cellular uptake of these peptides. These arginine-rich peptide vectors share many common features in internalization. However, there seem to be certain simultaneous dissimilarities observed in the modes of internalization among these peptides. In this review, the structural features of these arginine-rich peptide vectors have been focused on and the current understandings of their internalization mechanisms are summarized.
HUMAN APOLIPOPROTEIN MOLECULAR BIOLOGY AND GENETIC VARIATION (1985)

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