gebhart/patrepeval huggingface dataset:
Topology prediction of membrane proteins (1996)

A new method is described for prediction of protein membrane topology (intra- and extracellular sidedness) from multiply aligned amino acid sequences after determination of the membrane-spanning segments. The prediction technique relies on residue compositional differences in the protein segments exposed at each side of the membrane. Intra/extracellular ratios are calculated for the residue types Asn, Asp, Gly, Phe, Pro, Trp, Tyr, and Val, preferably found on the extracellular side, and for Ala, Arg, Cys, and Lys, mostly occurring on the intracellular side. The consensus over these 12 residue distributions is used for sidedness prediction. The method was developed with a test set of 42 protein families, for which all but one were correctly predicted with the new algorithm. This represents an improvement over predictions based on the widely used "positive-inside rule" and other techniques, where at least six mispredictions were observed for the same data set. Further, application of this and other methods to 12 protein families not in the test set still showed the better performance of the present technique, which was subsequently applied to another set of membrane protein families where the topology has yet to be determined.
The ets-Related Transcription Factor GABP Directs Bidirectional Transcription (2007)

Approximately 10% of genes in the human genome are distributed such that their transcription start sites are located less than 1 kb apart on opposite strands. These divergent gene pairs have a single intergenic segment of DNA, which in some cases appears to share regulatory elements, but it is unclear whether these regions represent functional bidirectional promoters or two overlapping promoters. A recent study showed that divergent promoters are enriched for consensus binding sequences of a small group of transcription factors, including the ubiquitous ets-family transcription factor GA-binding protein (GABP). Here we show that GABP binds to more than 80% of divergent promoters in at least one cell type. Furthermore, we demonstrate that GABP binding is correlated and associated with bidirectional transcriptional activity in a luciferase transfection assay. In addition, we find that the addition of a strict consensus GABP site into a set of promoters that normally function in only one direction significantly increases activity in the opposite direction in 67% of cases. Our findings demonstrate that GABP regulates the majority of divergent promoters and suggest that bidirectional transcriptional activity is mediated through GABP binding and transactivation at both divergent and nondivergent promoters.
Gene Silencing by Double‐Stranded RNA (Nobel Lecture) (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Encephalitogenic T cell clones specific for myelin basic protein. An unusual bias in antigen recognition. (1985)

Class II-restricted T cell clones specific for myelin basic protein (MBP) have been generated from PL/J and (PL/J X SJL/J)F1 [((PLSJ)F1] mice following sensitization to rat MBP. Of 17 T cell clones generated from (PLSJ)F1 mice, 5 are I-Au(A alpha uA beta u) restricted, one is restricted to I-As(A alpha sA beta s), 10 are restricted to hybrid I-A(u X s)F1 (A alpha sA beta u) determinants, and one clone is restricted to hybrid I-E(u X s) (E alpha uE beta s) molecules. Thus, of 16 I-A-restricted T cell clones generated from (PLSJ)F1 mice, only one is I-As-restricted, reflecting a lack of priming to MBP in association with I-As. T cell clones restricted to I-Au and to I-E (E alpha u E beta s) molecules recognize mouse (self) MBP. Furthermore, only the five T cell clones restricted to I-Au molecules recognize a determinant in common with mouse (self) MBP within the encephalitogenic N-terminal peptide. Three such I-Au restricted T cell clones, derived independently, cause paralysis in 100% of (PL/J X SJL/J)F1 mice tested. Acute, chronic unremitting, and chronic relapsing paralysis are all induced following injection of these clones. Administration of greater numbers of cloned T cells causes acute and fatal experimental allergic encephalomyelitis, while administration of lower numbers of cloned T cells is associated with chronic unremitting and relapsing paralysis. Paralysis induced with T cell clones shares many clinical, immunologic, and histologic aspects with human demyelinating diseases such as multiple sclerosis. Histopathology reveals perivascular lymphocytic infiltration, demyelination, and remyelination. These studies demonstrate the utility of T cell clones for analyzing the association between class II major histocompatibility complex molecules and disease susceptibility.
Chromatography of antihemophilic factor on diaminoalkane- and aminoalkane-derivatized Sepharose. (1982)

Antihemophilic factor was chromatographed on a homologous series of diaminoalkane- and aminoalkane-modified Sepharose beads. Both factor VIII procoagulant activity (VIII:C) and protein are retarded on these columns when compared to their elution on a column made of unmodified Sepharose. Longer chains bind VIII:C and protein more tightly than shorter chains. No bound activity could be eluted with ethylene glycol. Increasing ionic strength eluted VIII:C and protein from aminoalkane- as well as from alkane-Sepharose. It seems likely that hydrophobic, rather than ionic forces, are responsible for the binding of VIII:C to the latter carriers.
Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals (2011)

A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targets for vaccine design. HIV-1-infected subjects with potent cross-reactive serum neutralizing antibodies were identified by assaying sera from 308 subjects against a multiclade panel of 12 "tier 2" viruses (4 each of subtypes A, B, and C). Various neutralizing epitope specificities were determined for the top 9 neutralizers, including clade A-, clade B-, clade C-, and clade A/C-infected donors, by using a comprehensive set of assays. In some subjects, neutralization breadth was mediated by two or more antibody specificities. Although antibodies to the gp41 membrane-proximal external region (MPER) were identified in some subjects, the subjects with the greatest neutralization breadth targeted gp120 epitopes, including the CD4 binding site, a glycan-containing quaternary epitope formed by the V2 and V3 loops, or an outer domain epitope containing a glycan at residue N332. The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV-1 envelope glycoprotein.
The use of visual feedback, in particular mirror visual feedback, in restoring brain function (2009)

This article reviews the potential use of visual feedback, focusing on mirror visual feedback, introduced over 15 years ago, for the treatment of many chronic neurological disorders that have long been regarded as intractable such as phantom pain, hemiparesis from stroke and complex regional pain syndrome. Apart from its clinical importance, mirror visual feedback paves the way for a paradigm shift in the way we approach neurological disorders. Instead of resulting entirely from irreversible damage to specialized brain modules, some of them may arise from short-term functional shifts that are potentially reversible. If so, relatively simple therapies can be devised--of which mirror visual feedback is an example--to restore function.
Theory of communication. Part 1: The analysis of information (1946)

Hitherto communication theory was based on two alternative methods of signal analysis. One is the description of the signal as a function of time; the other is Fourier analysis. Both are idealizations, as the first method operates with sharply defined instants of time, the second with infinite wave-trains of rigorously defined frequencies. But our everyday experiences—especially our auditory sensations—insist on a description in terms of both time and frequency. In the present paper this point of view is developed in quantitative language. Signals are represented in two dimensions, with time and frequency as co-ordinates. Such two-dimensional representations can be called “information diagrams,” as areas in them are proportional to the number of independent data which they can convey. This is a consequence of the fact that the frequency of a signal which is not of infinite duration can be defined only with a certain inaccuracy, which is inversely proportional to the duration, and vice versa. This “uncertainty relation” suggests a new method of description, intermediate between the two extremes of time analysis and spectral analysis. There are certain “elementary signals” which occupy the smallest possible area in the information diagram. They are harmonic oscillations modulated by a “probability pulse.” Each elementary signal can be considered as conveying exactly one datum, or one “quantum of information.” Any signal can be expanded in terms of these by a process which includes time analysis and Fourier analysis as extreme cases.These new methods of analysis, which involve some of the mathematical apparatus of quantum theory, are illustrated by application to some problems of transmission theory, such as direct generation of single sidebands, signals transmitted in minimum time through limited frequency channels, frequency modulation and time-division multiplex telephony.
Functional Knockout of the Transient Outward Current, Long-QT Syndrome, and Cardiac Remodeling in Mice Expressing a Dominant-Negative Kv4 α Subunit (1998)

Abstract —A novel in vivo experimental strategy, involving cell type–specific expression of a dominant-negative K + channel pore-forming α subunit, was developed and exploited to probe the molecular identity of the cardiac transient outward K + current ( I to ). A point mutation (W to F) was introduced at position 362 in the pore region of Kv4.2 to produce a nonconducting mutant (Kv4.2W362F) subunit. Coexpression of Kv4.2W362F with Kv4.2 (or Kv4.3) attenuates the wild-type currents, and the effect is subfamily specific; ie, Kv4.2W362F does not affect heterologously expressed Kv1.4 currents. With the use of the α-myosin heavy chain promoter to direct cardiac-specific expression, several lines of Kv4.2W362F transgenic mice were generated. Electrophysiological recordings reveal that I to is selectively eliminated in ventricular myocytes isolated from transgenic mice expressing Kv4.2W362F, thereby demonstrating directly that the Kv 4 subfamily underlies I to in the mammalian heart. Functional knockout of I to leads to marked increases in action potential durations in ventricular myocytes and to prolongation of the QT interval in surface ECG recordings. In addition, a novel rapidly activating and inactivating K + current, which is not detectable in myocytes from nontransgenic littermates, is evident in Kv4.2W362F-expressing ventricular cells. Importantly, these results demonstrate that electrical remodeling occurs in the heart when the expression of endogenous K + channels is altered.
Reactions of tetrahalogeno-1,2-benzoquinones. Part III. Reaction of tetrachloro-1,2-benzoquinone with tetralones and naphthols: pathway to the condensates (1970)

With a view to understanding the mechanism of the formation of 6-methoxy-2,2-(tetrachloro-o-phenylenedioxy)-naphthalen-1 (2H)-one (IIIa) in the reaction of 6-methoxy-1-tetralone (Ia) with tetrachloro-1,2-benzoquinone (II), the reaction of (II) with various tetralones and naphthols has been studied. Reaction with either α-tetralone or α-naphthol gives 2,2-(tetrachloro-o-phenylenedioxy)naphthalen-1 (2H)-one (IIIb), whereas reaction with either β-tetralone or β-naphthol gives a mixture of (IIIb) and 1,1-(tetrachloro-o-phenylenedioxy)-naphthalen-2(1H)-one (IX), with the former predominating. Further, reactions of (II) with 7-methoxy-3,4-dihydrophenanthren-1(2H)-one and m-methoxyphenol gave respectively 7-methoxy-2,2-(tetrachloro-o-phenylenedioxy)phenanthren-1 (2H)-one (VII) and 3-methoxy-6,6-(tetrachloro-o-phenylenedioxy)cyclohexa-2,4-dien-1-one (VIII). Structures of all these compounds have been proved on the basis of i.r. and n.m.r. data. The pathway to the formation of the condensates (III) is discussed.
Glycosaminoglycan Mimetic Biomaterials. 2. Alkene- and Acrylate-Derivatized Glycopolymers via Cyanoxyl-Mediated Free-Radical Polymerization (2001)

Cyanoxyl (•OC⋮N)-mediated free-radical polymerization provides an effective and versatile method for engineering a diverse array of water-soluble glycopolymers with high saccharide contents and low polydispersity indexes (1.1 < Mw/Mn < 1.6). Cyanoxyl persistent radicals can be used as chain-growth moderators of the statistical copolymerization of acrylamide with either nonsulfated or sulfated N-acetyl-d-glucosamine-carrying alkene- and acrylate-derivatized unprotected glycomonomers. Moreover, monosaccharide-containing homopolymers can be prepared with some degree of control by polymerization of the acrylic glycomonomers.
Classification and Mutation Prediction from Non-Small Cell Lung Cancer Histopathology Images using Deep Learning (2017)

Abstract Visual analysis of histopathology slides of lung cell tissues is one of the main methods used by pathologists to assess the stage, types and sub-types of lung cancers. Adenocarcinoma and squamous cell carcinoma are two most prevalent sub-types of lung cancer, but their distinction can be challenging and time-consuming even for the expert eye. In this study, we trained a deep learning convolutional neural network (CNN) model (inception v3) on histopathology images obtained from The Cancer Genome Atlas (TCGA) to accurately classify whole-slide pathology images into adenocarcinoma, squamous cell carcinoma or normal lung tissue. Our method slightly outperforms a human pathologist, achieving better sensitivity and specificity, with ∼0.97 average Area Under the Curve (AUC) on a held-out population of whole-slide scans. Furthermore, we trained the neural network to predict the ten most commonly mutated genes in lung adenocarcinoma. We found that six of these genes – STK11, EGFR, FAT1, SETBP1, KRAS and TP53 – can be predicted from pathology images with an accuracy ranging from 0.733 to 0.856, as measured by the AUC on the held-out population. These findings suggest that deep learning models can offer both specialists and patients a fast, accurate and inexpensive detection of cancer types or gene mutations, and thus have a significant impact on cancer treatment.
Dynamic space management for user interfaces (2000)

We present a general approach to the dynamic representation of 2D space that is well suited for userinterface layout. We partition space into two distinct categories: full and empty. The user can explicitly specify a set of possibly overlapping upright rectangles that represent the objects of interest.
An overview of multi-carrier CDMA (2002)

We review new multiple access schemes based on a combination of code division and multi-carrier (also known as OFDM: orthogonal frequency division multiplexing) techniques, such as multi-carrier code division multiple access (MC-CDMA), multicarrier DS-CDMA and multitone CDMA (MT-CDMA). We discuss their advantages and disadvantages, and present some computer simulation results on the down-link bit error rate (BER) performance in a frequency selective slow Rayleigh fading channel. Code division and OFDM based multiple access schemes have drawn a lot of attention in the field of wireless personal and multimedia communications because of the need to transmit at a high data rate in a mobile environment.
Development and Characterization of an Acellular Human Pericardial Matrix for Tissue Engineering (2006)

This study aimed to produce an acellular human tissue scaffold with a view to recellularization with autologous cells to produce a tissue-engineered pericardium that can be used as a patch for cardiovascular repair. Human pericardia from cadaveric donors were treated sequentially with hypotonic buffer, SDS in hypotonic buffer, and a nuclease solution. Histological analysis of decellularized matrices showed that the human pericardial tissue retained its histioarchitecture and major structural proteins. There were no whole cells or cell fragments. There were no significant differences in the hydroxyproline (normal and denatured collagen) and glycosaminoglycan content of the tissue before and after decellularization (p > 0.05). There were no significant changes in the ultimate tensile strength after decellularization (p > 0.05). However, there was an increased extensibility when the tissue strips were cut parallel to the visualized collagen bundles (p = 0.005). No indication of contact or extract cytotoxicity was found when using human dermal fibroblasts and A549 cells. In summary, successful decellularization of the human pericardium was achieved producing a biocompatible matrix that retained the major structural components and strength of the native tissue.
WNT1 gene expression alters in heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+ prostate cancer stem cell spheroids. (2014)

It is possible to assume that intracellular signaling of WNT-related molecules in the nucleus and/or cytoplasm might play an important role but it is independent from increased ligand expression and this expression strongly differentiate CSCs and non-CSCs population. This unexpected expression could be important for CSCs behavior and targeting this pathway could have therapeutic implications in cancer.
Scalable Kernel Fusion for Memory-Bound GPU Applications (2014)

GPU implementations of HPC applications relying on finite difference methods can include tens of kernels that are memory-bound. Kernel fusion can improve performance by reducing data traffic to off-chip memory, kernels that share data arrays are fused to larger kernels where on-chip cache is used to hold the data reused by instructions originating from different kernels. The main challenges are a) searching for the optimal kernel fusions while constrained by data dependencies and kernels' precedences and b) effectively applying kernel fusion to achieve speedup. This paper introduces a problem definition and proposes a scalable method for searching the space of possible kernel fusions to identify optimal kernel fusions for large problems. The paper also proposes a codeless performance upper-bound projection model to achieve effective fusions. Results show that using the proposed scalable method for kernel fusion improved the performance of two real-world applications containing tens of kernels by 1.35x and 1.2x.
Dual-resonance monopole antenna with tuning stubs (2006)

A dual-resonance monopole antenna is proposed for application in mobile communications devices. The antenna is small in comparison with conventional monopole antennas as only one resonator is used to realise dual-resonance operation. The frequency ratio of the dual resonance is adjusted by employing a number of tuning stubs. It is demonstrated that GSM (Global System for Mobile Communications) tri-band operation including GSM900 (880–960 MHz), GSM1800 (1710–1880 MHz) and GSM1900 (1850–1990 MHz) can be achieved by using the monopole antenna with an overall size of 20×20×1 mm3 for a conventional handset.
A high throughput screening for rarely transcribed differentially expressed genes (1997)

A novel method combining elements of suppression subtractive hybridization with high throughput differential screening permits the efficient and rapid cloning of rarely transcribed differentially expressed genes. The experimental strategy virtually excludes the possibility of isolating false positive clones. The potential of the method is demonstrated by the isolation of 625 differentially expressed cDNAs from the metastatic adenocarcinoma cell line Bsp73-ASML when subtracted from its non-metastatic counterpart Bsp73-1AS. Northern analysis of 72 randomly selected clones demonstrated that 68 were differentially expressed with respect to Bsp73-ASML, indicating a true positive rate of 94%. Additionally, a large proportion of these clones represented rare transcripts as determined by the exposure time required to detect a signal. Sequence data indicated that of the 625 clones obtained, 92 clones scored perfect or near perfect matches with already known genes. Two hundred and eighty one clones scored between 60 and 95% homology to known human and mouse genes, whereas 252 clones scored no match with any sequences in the public databases. The method we describe is ideally suited whenever subtle changes in gene expression profiles need to be determined.
Shading-based refinement on volumetric signed distance functions (2015)

We present a novel method to obtain fine-scale detail in 3D reconstructions generated with low-budget RGB-D cameras or other commodity scanning devices. As the depth data of these sensors is noisy, truncated signed distance fields are typically used to regularize out the noise, which unfortunately leads to over-smoothed results. In our approach, we leverage RGB data to refine these reconstructions through shading cues, as color input is typically of much higher resolution than the depth data. As a result, we obtain reconstructions with high geometric detail, far beyond the depth resolution of the camera itself. Our core contribution is shading-based refinement directly on the implicit surface representation, which is generated from globally-aligned RGB-D images. We formulate the inverse shading problem on the volumetric distance field, and present a novel objective function which jointly optimizes for fine-scale surface geometry and spatially-varying surface reflectance. In order to enable the efficient reconstruction of sub-millimeter detail, we store and process our surface using a sparse voxel hashing scheme which we augment by introducing a grid hierarchy. A tailored GPU-based Gauss-Newton solver enables us to refine large shape models to previously unseen resolution within only a few seconds.
CHANGES IN THE PITUITARY‐TESTICULAR SYSTEM WITH AGE (1976)

In order to provide a comprehensive account of pituitary-testicular function in man, 466 subjects, ranging in age from 2 to 101 years, were studied to examine blood levels of the pituitary gonadotrophins (LH and FSH), the sex steroids testosterone and oestradiol, the binding capacity of the sex hormone binding globulin (SHBG), the free testosterone and oestradiol fractions, and the transfer constant for the peripheral conversion of testosterone to oestradiol. The results were compared with clinical indices of testicular size, sexual function and secondary sex hair distribution. Serum LH and FSH were low before puberty, increased in pubertal adolescents to levels somewhat above those of adults and subsequently increased progressively over the age of 40 years. Testosterone levels fell slowly after the age of 40, while there was a slight rise in plasma oestradiol with increasing age. FSH and testosterone showed small seasonal variations in young adult men, the lowest values being seen in winter. SHBG binding capacity was high in two prepubertal boys, fell in adult men, but increased in old age. Free testosterone and oestradiol levels fell in old age. The metabolic clearance rates (MCR) of testosterone and oestradiol also fell in old age, while the conversion of testosterone to oestradiol was increased. Many correlations were observed between various hormonal and clincial measurements. The evidence is consistent with a primary decrease in testicular function over the age of 40 years.