gebhart/patrepeval huggingface dataset:
Enhanced brain activity may precede the diagnosis of Alzheimer's disease by 30 years (2006)

Presenilin 1 (PSEN1) mutations cause autosomal dominant familial Alzheimer's disease (FAD). PSEN1 mutation carriers undergo the course of cognitive deterioration, which is typical for sporadic Alzheimer's disease but disease onset is earlier and disease progression is faster. Here, we sought to detect signs of FAD in presymptomatic carriers of the PSEN1 mutation (C410Y) by use of a neuropsychological examination, functional MRI during learning and memory tasks and MRI volumetry. We examined five non-demented members of a FAD family and 21 non-related controls. Two of the five family members were carrying the mutation; one was 20 years old and the other 45 years old. The age of clinical manifestation of FAD in the family studied here is $48 years. Neuropsychological assessments suggested subtle problems with episodic memory in the 20-yearold mutation carrier. The middle-aged mutation carrier fulfilled criteria for amnestic mild cognitive impairment. The 20-year-old mutation carrier exhibited increased, while the middle-aged mutation carrier exhibited decreased brain activity compared to controls within memory-related neural networks during episodic learning and retrieval, but not during a working-memory task. The increased memory-related brain activity in the young mutation carrier might reflect a compensatory effort to overcome preclinical neural dysfunction caused by first pathological changes. The activity reductions in the middle-aged mutation carrier might reflect gross neural dysfunction in a more advanced stage of neuropathology. These data suggest that functional neuroimaging along with tasks that challenge specifically those brain areas which are initial targets of Alzheimer's disease pathology may reveal activity alterations on a single-subject level decades before the clinical manifestation of Alzheimer's disease.
Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions (2014)

To understand how pairwise cellular interactions influence cellular architectures, we measured the levels of functional proteins associated with EGF receptor (EGFR) signaling in pairs of U87EGFR variant III oncogene receptor cells (U87EGFRvIII) at varying cell separations. Using a thermodynamics-derived approach we analyzed the cell-separation dependence of the signaling stability, and identified that the stable steady state of EGFR signaling exists when two U87EGFRvIII cells are separated by 80-100 μm. This distance range was verified as the characteristic intercellular separation within bulk cell cultures. EGFR protein network signaling coordination for the U87EGFRvIII system was lowest at the stable state and most similar to isolated cell signaling. Measurements of cultures of less tumorigenic U87PTEN cells were then used to correctly predict that stable EGFR signaling occurs for those cells at smaller cell-cell separations. The intimate relationship between functional protein levels and cellular architectures explains the scattered nature of U87EGFRvIII cells relative to U87PTEN cells in glioblastoma multiforme tumors.
Empirical relationships between protein structure and carboxyl pK<sub>a</sub> values in proteins (2002)

Relationships between protein structure and ionization of carboxyl groups were investigated in 24 proteins of known structure and for which 115 aspartate and 97 glutamate pK(a) values are known. Mean pK(a) values for aspartates and glutamates are < or = 3.4 (+/-1.0) and 4.1 (+/-0.8), respectively. For aspartates, mean pK(a) values are 3.9 (+/-1.0) and 3.1 (+/-0.9) in acidic (pI < 5) and basic (pI > 8) proteins, respectively, while mean pK(a) values for glutamates are approximately 4.2 for acidic and basic proteins. Burial of carboxyl groups leads to dispersion in pK(a) values: pK(a) values for solvent-exposed groups show narrow distributions while values for buried groups range from < 2 to 6.7. Calculated electrostatic potentials at the carboxyl groups show modest correlations with experimental pK(a) values and these correlations are not improved by including simple surface-area-based terms to account for the effects of desolvation. Mean aspartate pK(a) values decrease with increasing numbers of hydrogen bonds but this is not observed at glutamates. Only 10 pK(a) values are > 5.5 and most are found in active sites or ligand-binding sites. These carboxyl groups are buried and usually accept no more than one hydrogen bond. Aspartates and glutamates at the N-termini of helices have mean pK(a) values of 2.8 (+/-0.5) and 3.4 (+/-0.6), respectively, about 0.6 units less than the overall mean values.
Efficient Histogram Estimation for Smart Grid Data Processing With the Loglog-Bloom-Filter (2014)

With the emerging area of smart grids, one critical challenge faced by administrators of wide-area measurement systems is to analyze and model streaming data with limited resources on their embedded controllers. Usually, streaming data can be modeled as a multiset where each data item has its own frequency. In this paper, we study the problem on how to generate histograms of data items based on their frequency, so we can identify various issues such as power line tripping or line faults under constraints. The primary challenge for achieving this goal using conventional methods is that keeping an individual counter for each unique type of data is too memory-consuming, slow, and costly. In this paper, we describe a novel data structure and its associated algorithms, called the loglog bloom filter, for this purpose. This data structure extends the classical bloom filter with a recent technique called probabilistic counting, so it can effectively generate histograms for streaming data in one pass with sub-linear overhead. Therefore, this method is suitable for data processing in smart grids, where limited computational resources are available on the controllers. We analyze the performance, trade-offs, and capacity of this data structure, and evaluate it with real data traces collected through the frequency disturbance recorders deployed for the FNET/GridEye infrastructure. We demonstrate that this method can identify the frequencies of all unique items with high accuracy and low memory overhead, so that data outliers can be conveniently identified.
A phorbol ester/diacylglycerol-binding protein encoded by the unc-13 gene of Caenorhabditis elegans. (1991)

Mutations in the unc-13 gene cause diverse defects in the nervous system of the nematode Caenorhabditis elegans. Molecular cloning of the gene and sequencing of the cDNA revealed that the product encodes a protein, 1734 amino acids in length, with a central domain with sequence similarity to the regulatory region of protein kinase C. The domain was expressed in Escherichia coli and shown to bind specifically to a phorbol ester in the presence of calcium; diacylglycerol inhibited the binding in a competitive manner. These findings confirm that the unc-13 gene product has binding sites similar to those of protein kinase C and may be a component of an alternative transduction pathway of the diacylglycerol signal to a different effector function in the nervous system.
Customer network reconfiguration applications utilizing digital cross-connect systems (2003)

The author discusses four customer applications based on digital-cross-connect (DCS) systems. The applications which entail customer control of DCS, are: citywide Centrex with adaptive differential pulse-code modulation, disaster recovery, and network optimization, the use of compressed voice and compressed video networks, and cellular radio.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach (2012)

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland) is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.
Perforating Disorders: Summary Notes (2000)

The intention of the Summary Notes section is to provide the practitioner and trainee with a current, concise reference source to dermatologic diseases and to serve as a form of Continuing Medical Education. Each installment will deal with a specific disease. When included, the pretest questions indicate some of the areas to be covered and will challenge your present knowledge of the material before reading further. The self-assessment post-test questions appear on page 18; the answers are on page 25.
How will Autonomous Vehicle technologies affect driver liability and overall insurance? (2015)

Presents a collection of slides covering the following topics: autonomous vehicle technologies; driver liability; insurance; UK autodrive; advanced driver aids; driverless cars; risk pricing; and cost-benefit analysis.
An α- <scp>l</scp> -Arabinofuranosidase from <i>Trichoderma reesei</i> Containing a Noncatalytic Xylan-Binding Domain (1999)

L-Sorbose, an excellent cellulase and xylanase inducer from Trichoderma reesei PC-3-7, also induced alpha-L-arabinofuranosidase (alpha-AF) activity. An alpha-AF induced by L-sorbose was purified to homogeneity, and its molecular mass was revealed to be 35 kDa (AF35), which was not consistent with that of the previously reported alpha-AF. Another species, with a molecular mass of 53 kDa (AF53), which is identical to that of the reported alpha-AF, was obtained by a different purification procedure. Acid treatment of the ammonium sulfate-precipitated fraction at pH 3.0 in the purification steps or pepsin treatment of the purified AF53 reduced the molecular mass to 35 kDa. Both purified enzymes have the same enzymological properties, such as pH and temperature effects on activity and kinetic parameters for p-nitrophenyl-alpha-L-arabinofuranoside (pNPA). Moreover, the N-terminal amino acid sequences of these enzymes were identical with that of the reported alpha-AF. Therefore, it is obvious that AF35 results from the proteolytic cleavage of the C-terminal region of AF53. Although AF35 and AF53 showed the same catalytic constant with pNPA, the former showed drastically reduced specific activity against oat spelt xylan compared to the latter. Furthermore, AF53 was bound to xylan rather than to crystalline cellulose (Avicel), but AF35 could not be bound to any of the glycans. These results suggest that AF53 is a modular glycanase, which consists of an N-terminal catalytic domain and a C-terminal noncatalytic xylan-binding domain.
Co-opting Intracellular Proteins for Cell-Specific Gene Manipulation (2015)

Studies of complex multicellular organisms would benefit from the ability to selectively manipulate the activities of any cell type of interest. Our ability to achieve this is currently limited by technology and available resources. Here, I explore the artificial use of intracellular proteins as signals for conferring cell specificity in gene manipulation. The Green Fluorescent Protein (GFP) is a useful marker of gene expression and thousands of transgenic GFP reporter lines have been made to label different cell types, particularly in the mouse nervous system. However, the utility of transgenic GFP reporter lines is limited to labeling purposes. I exploited this resource for cell-specific gene manipulation by constructing synthetic systems that become biologically active upon interaction with GFP. Using GFP-binding nanobodies derived from Camelid antibodies, I co-opted GFP as a scaffold protein to bring together complementary split proteins that, when in a complex, can regulate processes such as transcription and DNA recombination. I demonstrate the utility of these systems for selectively manipulating GFP-expressing cells in the mouse nervous system and in zebrafish, for applications such as developmental perturbations, electrophysiology and optogenetic interrogation of neural circuits. To reduce the complexity of GFP-dependent systems, I developed a binary system in which GFP binds to a destabilized nanobody and, in doing so, stabilizes expression level of an output protein fused to the nanobody. I show that this approach could be used to construct fluorescent sensors and functional effectors that are only active in the presence of the intracellular antigen. This strategy can be extended to target a different intracellular protein, the HIV C-terminal domain (CTD), for intracellular antigen-inducible protein stabilization. The strategy used to generate CTD-inducible protein sensors may potentially be generalized to facilitate rapid design of protein-responsive sensors and effectors, based on elucidation of an amino acid code that can be applied across conserved protein scaffolds or antibody frameworks regardless of antigen identity. Thus, my work expands the experimental paradigm for manipulation of specific cell types in multicellular organisms and provides tools and approaches for increasingly precise analysis of biological processes in transgenic and wildtype animals.
Identification of HLA class I dependent immunogenic peptides from clonotypic TCRβ expressed in cutaneous T‐cell lymphoma (2006)

Abstract The clonotypic T‐cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T‐cell lymphoma (CTCL). We identified T‐cell epitopes from the rearranged TCR β chain of the malignant T‐cell population by the “reverse immunology” approach. Peptide‐specific T‐cell lines were generated against predicted epitopes and tested for the recognition of tumor cells and cells transfected with the full‐length DNA coding for TCRV β chain. Two peptides derived from the clonotypic TCRVβ of a HLA‐A2 positive patient could induce peptide‐specific T cells from peripheral blood mononuclear cells of healthy donors and the patient as assessed by IFN‐γ ELISpot assay. Furthermore, the reactive CTLs efficiently recognized autologous Sézary tumor cells, as well as HLA‐A2 positive 293 cells transfected with recombinant plasmid expressing the corresponding TCRVβ29 protein. Similar results were obtained in a HLA‐A3+ patient for TCRVβ7‐Jβ2.7. In conclusion, our experiments show that the TCR β chain harbors epitopes suitable as targets for specific vaccination which might be a promising approach for the specific immunotherapy of cutaneous T‐cell lymphoma patients. © 2006 Wiley‐Liss, Inc.
General Theory of Optimal Error Algorithms and Analytic Complexity. Part A. General Information Model. (1977)

This is the first of a series of papers constructing an information based general theory of optimal errors and analytic computational complexity. Among the applications are such traditionally diverse areas as approximation, boundary-value problems, quadrature, and nonlinear equations in a finite or infinite dimensional space. Traditionally algorithms are often derived by ad hoc criteria. The information based theory rationalizes the synthesis of algorithms by showing how to construct algorithms which minimize or nearly minimize the error. For certain classes of problems it shows how to construct algorithms (linear optimal error algorithms) which enjoy essentially optimal complexity with respect to all possible algorithms. The existence of strongly non-computable problems is demonstrated. In contrast with the gap theorem of recursively computable functions it is shown that every monotonic real function is the complexity of some problem.
Structure and arrangement of the cholera toxin genes in Vibrio cholerae O139 (1994)

The sequence of the ctxB gene encoding the B subunit of cholera toxin has been determined for a strain of Vibrio cholerae of the novel O139 serotype associated with recent outbreaks of severe cholera throughout South-East Asia and found to be identical to the ctxB gene in V. cholerae O1 of the E1 Tor biotype. Analyses by Southern hybridization and PCR showed that all strains of the O139 serotype V. cholerae tested carried cholera toxin genes and other gene associated with a virulence cassette DNA region at two loci identical or homologous to those identified in the Classical rather than the E1 Tor biotype of V. cholerae serotype O1 although these loci in O139 could reside on restriction fragments of variable size.
Abortive initiation by bacteriophage T3 and T7 RNA polymerases under conditions of limiting substrate (1989)

Nucleic Acids Research, 17, 1605–1618 (1989) The Figure 2 legend should read: In order, from left to right, the Concentrations of these substrates were 400, 200, 100, 50. 25, and 12.5 μM. The Figure 3 legend should read: Unless otherwise noted the concentration of all ribonucleoside triphosphates was 400 μM: in lanes marked C or U the concentration of CTP or UTP was 10 μM. The Figure 4 legend should read: Panel A. Hae II restriction fragments of T7 DNA (0.25 μg) were incubated with a four-fold or eight-fold molar excess of RNA polymerase, as indicated by the numbers above the lane. The column headings in Table I should read: UTP concn (μM) CTP eonn (μM)
Opioid antagonists for prevention and treatment of opioid-induced gastrointestinal effects (2010)

The availability of opioid receptor antagonists with restricted access to the central nervous system provides a novel opportunity to specifically control opioid-induced constipation and other peripheral adverse effects of opioid analgesics. Further studies are needed to evaluate the long-term efficacy, safety and cost-effectiveness of this approach.
The Medicago Genome Initiative: a model legume database (2001)

The Medicago Genome Initiative (MGI) is a database of EST sequences of the model legume MEDICAGO: truncatula. The database is available to the public and has resulted from a collaborative research effort between the Samuel Roberts Noble Foundation and the National Center for Genome Resources to investigate the genome of M.truncatula. MGI is part of the greater integrated MEDICAGO: functional genomics program at the Noble Foundation (http://www.noble.org ), which is taking a global approach in studying the genetic and biochemical events associated with the growth, development and environmental interactions of this model legume. Our approach will include: large-scale EST sequencing, gene expression profiling, the generation of M.truncatula activation-tagged and promoter trap insertion mutants, high-throughput metabolic profiling, and proteome studies. These multidisciplinary information pools will be interfaced with one another to provide scientists with an integrated, holistic set of tools to address fundamental questions pertaining to legume biology. The public interface to the MGI database can be accessed at http://www.ncgr.org/research/mgi.
Scene warping: Layer-based stereoscopic image resizing (2012)

This paper proposes scene warping, a layer-based stereoscopic image resizing method using image warping. The proposed method decomposes the input stereoscopic image pair into layers according to the depth and color information. A quad mesh is placed onto each layer to guide the image warping for resizing. The warped layers are composited by their depth orders to synthesize the resized stereoscopic image. We formulate an energy function to guide the warping for each layer so that the composited image avoids distortions and holes, maintains good stereoscopic properties and contains as many important pixels as possible in the reduced image space. The proposed method offers the advantages of less discontinuous artifacts, less-distorted objects, correct depth ordering and enhanced stereoscopic quality. Experiments show that our method compares favorably with existing methods.
Simplified Measurement of Intra-Access Pressure (1996)

Normalized intra-access pressure (PIA), expressed as the access pressure/systemic blood pressure, detects venous outlet stenosis and correlates with access blood flow. General use of (PIA) is limited by time, special equipment needs, and cost. We therefore correlated pressure measurements from the venous drip chamber (PDC of Fresenius H-machines and from an external transducer, P tau, for blood flows (BFR) of 0 to 400-500 ml/min. Measurements were conducted 2-3 weeks apart in a cohort of 33 patients. PDC = -21 + 1.28 P tau; PDC = P tau = 75 mmHg at BFR = 146 ml/min. The major determinant of P tau at BFR = 0 was access type and venous outflow problems. The difference between P tau and PDC (delta = offset) was 17 +/- 1 mmHg (range, 2-43); delta correlated with the height difference between the two sites. Differences in systemic blood pressure, zero calibration, and hydrostatic pressure accounted for 90% of the variance between replicate measurements of PDC. Detection of outlet stenosis was compared by using PIA calculated from P tau and from PDC + 17. Only three of 66 measurements using the latter produced misclassification, and never on replicate measurements. P tau and PDC measurements in 62 additional patients showed a persistent offset of 17 mmHg. The authors conclude that PDC at BFR = 0 can be used to monitor prospectively prosthetic bridge grafts for stenosis as long as the offset for a particular dialysis machine is determined.
Dark energy: A brief review (2013)

The problem of dark energy is briefly reviewed in both theoretical and observational aspects. In the theoretical aspect, dark energy scenarios are classified into symmetry, anthropic principle, tuning mechanism, modified gravity, quantum cosmology, holographic principle, back-reaction and phenomenological types. In the observational aspect, we introduce cosmic probes, dark energy related projects, observational constraints on theoretical models and model independent reconstructions.
Using Sesame to Secure Web Based Applications on an Intranet (1999)

The use of web technology within organisational Intranets is increasing. The combination of a standardised interface and the security features provided by TLS have made web technology very attractive. The TLS technology however has some limitations, especially in its lack of access control functionality. This paper focusses on alternatives to provide improved security services to web based applications. The SESAME security architecture is shown to provide all of the TLS security services, with the addition of other services such as the access control service. Also because SESAME uses the connection based GSS-API which is the same paradigm used by TLS, it is shown to be a suitable replacement. Unfortunately because web servers and web browsers do not provide hooks for replacing the TLS security technology, SESAME is not easily used. Two alternatives are therefore considered that overcome this limitation: a new proposal before the IETF of extending TLS to carry attribute certificates and a hybrid solution built by the authors.