gebhart/patrepeval huggingface dataset:
An integrated approach to the analysis and modeling of protein sequences and structures. III. A comparative study of sequence conservation in protein structural families using multiple structural alignments (2000)

The information required to generate a protein structure is contained in its amino acid sequence, but how three-dimensional information is mapped onto a linear sequence is still incompletely understood. Multiple structure alignments of similar protein structures have been used to investigate conserved sequence features but contradictory results have been obtained, due, in large part, to the absence of subjective criteria to be used in the construction of sequence profiles and in the quantitative comparison of alignment results. Here, we report a new procedure for multiple structure alignment and use it to construct structure-based sequence profiles for similar proteins. The definition of "similar" is based on the structural alignment procedure and on the protein structural distance (PSD) described in paper I of this series, which offers an objective measure for protein structure relationships. Our approach is tested in two well-studied groups of proteins; serine proteases and Ig-like proteins. It is demonstrated that the quality of a sequence profile generated by a multiple structure alignment is quite sensitive to the PSD used as a threshold for the inclusion of proteins in the alignment. Specifically, if the proteins included in the aligned set are too distant in structure from one another, there will be a dilution of information and patterns that are relevant to a subset of the proteins are likely to be lost. In order to understand better how the same three-dimensional information can be encoded in seemingly unrelated sequences, structure-based sequence profiles are constructed for subsets of proteins belonging to nine superfolds. We identify patterns of relatively conserved residues in each subset of proteins. It is demonstrated that the most conserved residues are generally located in the regions where tertiary interactions occur and that are relatively conserved in structure. Nevertheless, the conservation patterns are relatively weak in all cases studied, indicating that structure-determining factors that do not require a particular sequential arrangement of amino acids, such as secondary structure propensities and hydrophobic interactions, are important in encoding protein fold information. In general, we find that similar structures can fold without having a set of highly conserved residue clusters or a well-conserved sequence profile; indeed, in some cases there is no apparent conservation pattern common to structures with the same fold. Thus, when a group of proteins exhibits a common and well-defined sequence pattern, it is more likely that these sequences have a close evolutionary relationship rather than the similarities having arisen from the structural requirements of a given fold.
Molecular defects in coagulation Factor VIII and their impact on Factor VIII function (2002)

Molecular defects in Factor VIII (FVIII), such as haemophilia A-related mutations or denaturative conformational changes, may affect the stability of FVIII as well as its interactions with physiological activators, von Willebrand Factor, phospholipid, or conformationally sensitive antibodies. We summarize the contemporary assays which allow identification of impaired functional interactions of FVIII that cause a reduction or loss of its cofactor activity and/or increased immunogenicity. These assays can potentially be used for detection of molecular defects in FVIII and elucidation of the function impaired by these defects.
Patterns of Immunodominance in HIV-1–specific Cytotoxic T Lymphocyte Responses in Two Human Histocompatibility Leukocyte Antigens (HLA)-identical Siblings with HLA-A*0201 Are Influenced by Epitope Mutation (1997)

Primary human immunodeficiency virus (HIV) infection is controlled principally by HIV-specific cytotoxic T lymphocytes (CTL) to a steady-state level of virus load, which strongly influences the ultimate rate of progression to disease. Epitope selection by CTL may be an important determinant of the degree of immune control over the virus. This report describes the CTL responses of two HLA-identical hemophiliac brothers who were exposed to identical batches of Factor VIII and became seropositive within 10 wk of one another. Both have HLA-A*0201. The CTL responses of the two siblings were very dissimilar, one donor making strong responses to two epitopes within p17 Gag (HLA-A*0201-restricted SLYNTVATL and HLA-A3-restricted RLRPGGKKK). The sibling responded to neither epitope, but made strong responses to two epitopes presented by HLA-B7. This was not the result of differences in presentation of the epitopes. However, mutations in both immunodominant epitopes of the p17 Gag responder were seen in proviral sequences of the nonresponder. We then documented the CTL responses to two HLA-A*0201-restricted epitopes, in Gag (SLYNTVATL) and Pol (ILKEPVHGV) in 22 other HIV-infected donors with HLA-A*0201. The majority (71%) generated responses to the Gag epitope. In the 29% of donors failing to respond to the Gag epitope in standard assays, there was evidence of low frequency memory CTL responses using peptide stimulation of PBMC, and most of these donors also showed mutations in or around the Gag epitope. We concluded that HLA class I genotype determines epitope selection initially but that mutation in immunodominant epitopes can profoundly alter the pattern of CTL response.
Synthesis and characterization of ‘calixsalens’: a new class of macrocyclic chiral ligands (1999)

Template directed reaction of dialdehydes and (R,R)- or (S,S)-1,2-diaminocyclohexane affords a practical route to chiral, metal-free macrocyclic salen dimers which have a novel calixarene-like structure and show catalytic activity for enantioselective epoxidation of unfunctionalized alkenes in the presence of MnIII–NaOCl (aq.).
Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species 1 (1997)

Our laboratory has reported that glucose is essential for glycolytic enzyme induction and proliferation of mitogen-activated rat thymocytes (41). Here we show that: 1) Resting thymocytes meet their ATP demand mainly by oxidative glucose breakdown (88%), whereas proliferating thymocytes produce 86% by glycolytic degradation of glucose to lactate and only 14% by oxidation to CO2 and water. 2) In contrast to nonstimulated resting thymocytes, production of PMA primed reactive oxygen species (ROS) in the proliferating cells is nearly abolished. 3) Consistent with this finding, no ROS formation is observed in proliferating human promyelocytic HL-60 cells, whereas differentiated, nonproliferating HL-60 cells exert a marked response upon priming with PMA. 4) The observed reduction of ROS formation by resting thymocytes incubated with pyruvate suggests a function of pyruvate as an H(2)O(2) scavenger. 5) The respiratory chain is a potential origin for ROS because inhibitors of the mitochondrial electron transport strongly reduce H(2)O(2) production by resting thymocytes. The results are discussed in the context of aerobic glycolysis by proliferating cells being a means to minimize oxidative stress during the phases of the cell cycle where maximally enhanced biosynthesis and cell division do occur.
Molecular and cellular interactions in rheumatoid synovium (1996)

There is growing evidence that distinct molecular and cellular interactions in the rheumatoid synovium result in a complex cascade of pathophysiologic events. These interactions finally lead to progressive joint destruction, in a way that is different from all other joint diseases. Keystones are inflammation, proliferation of synovial cells, and attachment and invasion of synovial fibroblasts (in)to adjacent cartilage and bone, mediated by continuous release of matrix-degrading enzymes. Advances in molecular biology have provided numerous new data on the rheumatoid arthritis interaction cascade. Major research topics involve the balance of proinflammatory and inhibitory cytokines, the role of adhesion molecules in attachment of synovial fibroblasts to cartilage, and the localization of various matrix-degrading enzymes in the synovial lining. The results of the research reviewed here also provide a basis for future therapies including gene therapy.
Topical L-Ascorbic Acid: Percutaneous Absorption Studies (2001)

Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics.
History of Science Teaching in England. By D. M. TurnerM.A., B.Sc.(Lond.), Head of Science Department, Wycombe Abbey School; Research Assistant, University College, London. (London: Chapman & Hall, Ltd.1927. Pp. x + 208. Price 7s. 6d.) (1928)

History of Science Teaching in England. By D. M. TurnerM.A., B.Sc.(Lond.), Head of Science Department, Wycombe Abbey School; Research Assistant, University College, London. (London: Chapman &amp; Hall, Ltd.1927. Pp. x + 208. Price 7s. 6d.) - Volume 3 Issue 10
Transfusion-transmissible infections (1998)

Infectious agents, including viruses, bacteria, and parasites, can be transmitted by human blood products. Of major importance are viruses such as human immunodeficiency virus types 1 and 2 (HIV-1/2), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic virus types I and II (HTLV-I/II). Also, other viruses such as cytomegalovirus, Epstein-Barr virus, human parvovirus B19, and hepatitis A and G viruses can be transmitted by blood products. Various methods are used to prevent transmission of blood-borne agents to recipients, such as donor selection, testing donated blood for various infectious agents, and viral inactivation of plasma derivatives. With all these precautionary measures, the estimated risk for infection by screened blood components in Europe and the United States is approximately 1 in 50,000 to 1.6 million (for HBV, HCV, and HIV-1/2) transfused blood components. In the future, the safety of blood components may be increased by testing donated blood by nucleic acid amplification techniques and by photochemical decontamination of cellular blood components.
Tau: The Center of a Signaling Nexus in Alzheimer's Disease (2016)

Tau is a microtubule-associated protein whose misfolding, hyper-phosphorylation, loss of normal function and toxic gain of function are linked to several neurodegenerative disorders, including Alzheimer's disease (AD). This review discusses the role of tau in amyloid-β (Aβ) induced toxicity in AD. The consequences of tau dysfunction, starting from the axon and concluding at somadendritic compartments, will be highlighted.
DANTES: an expert system for real-time network troubleshooting (1987)

Today&amp;apos;s computer networks are large and complex. Their day-to-day operation and maintenance can benefit from the support of an expert system, mainly as an aid in troubleshooting. Network troubleshooting has characteristics, like incomplete data, high rate of events, simultaneous presence of several problems, which raise interesting problems in the development of an expert system. DANTES is an expert system designed to provide real-time assistance to network operators. This paper presents the system and stresses the development issues that are peculiar to network troubleshooting. Of particular importance are performance of inference in real-time, multi-problem handling, and consideration of time in reasoning and revision of belief Dealing with such issues and especially with real-time efficiency is primarily a question of system design. This has implications for the knowledge base organization, reasoning mechanism, and recording of deductions. 1.
Measurement of percent carboxyhemoglobin with pulse-oximetry technique (1988)

Computer simulations based on the photon diffusion theory are carried out to analyze the feasibility of measuring the percent carboxyhemoglobin (%HbCO) using the pulse-oximetry technique. A series of in vitro experiments using a mechanical pulser to simulate the pumping effect of the heart is performed. Both the theoretical and the experimental data show that a pulse-oximetry technique using multiple wavelengths can be applied for the measurement of %HbCO.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Exploratory Data Analysis: Past, Present and Future (1993)

The 1971-1977 early formulation of Exploratory Data Analysis, in terms of (a) results of some of its techniques and considerations which underlay, at various depths, the choices realized in the books. The 1991-1995 development of Exploratory Analysis of Variance, described in its simplest (two- way table) form and barely sketched in general. Discussion of the changes in apparent philosophy caused by the need to communicate more complicated things, notches, hints, the likely impact on a revised edition of Exploratory Data Analysis 1977. Dreams and targets for what might happen in 1996-2005, with emphasis on Exploratory Regression and the combined use of multiple description.
Targeting of Nonexpressed Genes in Embryonic Stem Cells Via Homologous Recombination (1989)

Gene targeting via homologous recombination-mediated disruption in murine embryonic stem (ES) cells has been described for a number of different genes expressed in these cells; it has not been reported for any nonexpressed genes. Pluripotent stem cell lines were isolated with homologously recombined insertions at three different loci: c-fos, which is expressed at a low level in ES cells, and two genes, adipsin and adipocyte P2 (aP2), which are transcribed specifically in adipose cells and are not expressed at detectable levels in ES cells. The frequencies at which homologous recombination events occurred did not correlate with levels of expression of the targeted genes, but did occur at rates comparable to those previously reported for genes that are actively expressed in ES cells. Injection of successfully targeted cells into mouse blastocysts resulted in the formation of chimeric mice. These studies demonstrate the feasibility of altering genes in ES cells that are expressed in a tissue-specific manner in the mouse, in order to study their function at later developmental stages.
Human Scribble (Vartul) Is Targeted for Ubiquitin-Mediated Degradation by the High-Risk Papillomavirus E6 Proteins and the E6AP Ubiquitin-Protein Ligase (2000)

The high-risk human papillomavirus (HPV) E6 proteins stimulate the ubiquitination and degradation of p53, dependent on the E6AP ubiquitin-protein ligase. Other proteins have also been shown to be targeted for degradation by E6, including hDlg, the human homolog of the Drosophila melanogaster Discs large (Dlg) tumor suppressor. We show here that the human homolog of the Drosophila Scribble (Vartul) (hScrib) tumor suppressor protein is also targeted for ubiquitination by the E6-E6AP complex in vitro and that expression of E6 induces degradation of hScrib in vivo. Characterization of the E6AP-E6-hScrib complex indicated that hScrib binds directly to E6 and that the binding is mediated by the PDZ domains of hScrib and a carboxyl-terminal epitope conserved among the high-risk HPV E6 proteins. Green fluorescent protein-hScrib was localized to the periphery of MDCK cells, where it colocalized with ZO-1, a component of tight junctions. E6 expression resulted in loss of integrity of tight junctions, as measured by ZO-1 localization, and this effect was dependent on the PDZ binding epitope of E6. Thus, the high-risk HPV E6 proteins induce the degradation of the human homologs of two Drosophila PDZ domain-containing tumor suppressor proteins, hDlg and hScrib, both of which are associated with cell junction complexes. The fact that Scrib/Vart and Dlg appear to cooperate in a pathway that controls Drosophila epithelial cell growth suggests that the combined targeting of hScrib and hDlg is an important component of the biologic activity of high-risk HPV E6 proteins.
Tamper resistance: a cautionary note (1996)

An increasing number of systems, from pay-TV to electronic purses, rely on the tamper resistance of smartcards and other security processors. We describe a number of attacks on such systems -- some old, some new and some that are simply little known outside the chip testing community. We conclude that trusting tamper resistance is problematic; smartcards are broken routinely, and even a device that was described by a government signals agency as &amp;apos;the most secure processor generally available&amp;apos; turns out to be vulnerable. Designers of secure systems should consider the consequences with care.
Purifying Noisy Entanglement Requires Collective Measurements (1998)

Known entanglement purification protocols for mixed states use collective measurements on several copies of the state in order to increase the entanglement of some of them. We address the question of whether it is possible to purify the entanglement of a state by processing each copy separately. While this is possible for pure states, we show that this is impossible, in general, for mixed states. The importance of this result both conceptually and for experimental realization of purification is discussed. We also give explicit invariants of an entangled state of two qubits under local actions and classical communication.
Antibody–cytokine fusion proteins: applications in cancer therapy (2008)

Multiple antibody-cytokine fusion proteins have demonstrated significant antitumor activity as direct therapeutics or as adjuvants of cancer vaccines in preclinical studies, paving the way for their clinical evaluation.
Modal Engineering for MEMS Devices: Application to Galvos and Scanners (2020)

Optical systems typically use galvanometers (aka galvos) and scanners. Galvos move optical elements such as mirrors, quasi-statically, from one static position to another, and an important figure of merit is their step-settle relaxation time. Scanners move in an oscillatory fashion, typically at the device resonant frequency. MEMS devices, which have many advantages and are often used in such optical systems, are typically high Q devices. Moving from one position to another for a galvo or one frequency/amplitude to another for scanners, can take many periods to settle following the ring down. During these transitions, the optical system is inactive and the time is not being efficiently used. In this article we show how a novel class of open loop control algorithms can be used to rapidly change position, frequency and amplitude, typically in well under the period of the device. We show how the MEMS designer can excite, with complete, high-speed control, a vibrational mode of the system. We call this modal engineering, the ability to control the modes of the system in a practical, fast way. This control of the modes is accomplished with open loop control algorithms.
The PROSITE database (2005)

The PROSITE database consists of a large collection of biologically meaningful signatures that are described as patterns or profiles. Each signature is linked to a documentation that provides useful biological information on the protein family, domain or functional site identified by the signature. The PROSITE database is now complemented by a series of rules that can give more precise information about specific residues. During the last 2 years, the documentation and the ScanProsite web pages were redesigned to add more functionalities. The latest version of PROSITE (release 19.11 of September 27, 2005) contains 1329 patterns and 552 profile entries. Over the past 2 years more than 200 domains have been added, and now 52% of UniProtKB/Swiss-Prot entries (release 48.1 of September 27, 2005) have a cross-reference to a PROSITE entry. The database is accessible at http://www.expasy.org/prosite/.
New targeted therapies for non-small-cell lung cancer (2009)

Advances in the understanding of non-small-cell lung cancer biology have led to the clinical development of biological therapies targeting molecular mechanisms underlying cancer growth and survival of this disease. In some cases, such strategies have significantly improved the outcome of advanced non-small-cell lung cancer in combination with platinum-based chemotherapy, as for the monoclonal antibodies cetuximab and bevacizumab directed against the EGF receptor and VEGF, respectively. In others, they have found a place in therapy in the management of pretreated patients, as for the EGF receptor tyrosine kinase inhibitors gefitnib and erlotinib. Importantly, the recognition that certain clinical or biological characteristics predict for increased sensitivity to treatment has highlighted the importance of patient selection when designing clinical trials with these agents. This review is structured in order to summarize the targeted therapies currently used for advanced non-small-cell lung cancer. In the la...
Drosophila cells use nanotube-like structures to transfer dsRNA and RNAi machinery between cells (2016)

Tunnelling nanotubes and cytonemes function as highways for the transport of organelles, cytosolic and membrane-bound molecules, and pathogens between cells. During viral infection in the model organism Drosophila melanogaster, a systemic RNAi antiviral response is established presumably through the transport of a silencing signal from one cell to another via an unknown mechanism. Because of their role in cell-cell communication, we investigated whether nanotube-like structures could be a mediator of the silencing signal. Here, we describe for the first time in the context of a viral infection the presence of nanotube-like structures in different Drosophila cell types. These tubules, made of actin and tubulin, were associated with components of the RNAi machinery, including Argonaute 2, double-stranded RNA, and CG4572. Moreover, they were more abundant during viral, but not bacterial, infection. Super resolution structured illumination microscopy showed that Argonaute 2 and tubulin reside inside the tubules. We propose that nanotube-like structures are one of the mechanisms by which Argonaute 2, as part of the antiviral RNAi machinery, is transported between infected and non-infected cells to trigger systemic antiviral immunity in Drosophila.
Generation of capsule‐deficient Neisseria meningitidis strains by homologous recombination (1990)

Capsule-deficient mutants of Neisseria meningitidis serogroup B strain B1940 were constructed by allelic replacement using the plasmids pMF120 and pMF121, which contain the flanking regions of the gene locus for the biosynthesis pathway of the group B meningococcal capsular polysaccharide. Southern blot analysis of chromosomal DNA of the capsule-deficient meningococcal strains confirmed the generation of large deletions in the chromosomal cps gene complex. The same strategy proved useful in constructing meningococcal strains with capsular types A, C, W135, Y and Z.