gebhart/patrepeval huggingface dataset:
PIKing the Right Patient (2010)

HER2 amplification and PIK3CA mutation were validated as biomarkers for sensitivity to the single-agent phosphoinositide 3-kinase (PI3K) inhibitor, GDC-0941, in breast cancer models. A novel expression profile was developed to identify other breast cancers sensitive to PI3K inhibitors. These expression studies highlighted feedback networks connecting TORC1, PI3K, and mitogen-activated protein kinase (MAPK) pathways, and underscored the potential for combination therapies.
CLINICAL AND NEUROPATHOLOGICAL CRITERIA FOR THE DIAGNOSIS AND STAGING OF DIABETIC POLYNEUROPATHY (1985)

Scored symptoms, neurological deficits, detection threshold of cutaneous sensation and parameters of nerve conduction were compared with quantitated neuropathological abnormalities in the sural nerve in 47 healthy subjects and 36 diabetic patients, 32 with and 4 without neuropathy. The fifth percentile line of a new Index of Pathology, which combines loss of myelinated fibres and abnormality of the remaining fibres, was found to provide a sensitive and reliable minimum neuropathological criterion for the diagnosis of polyneuropathy. Abnormality, as assessed by two clinical evaluations, similarly separated healthy subjects and diabetic patients into those with and without neuropathy. For the detection of diabetic polyneuropathy, vibration sense was more sensitive than touch-pressure or thermal cooling. Abnormalities of nerve conduction were found to be both sensitive and reliable in the detection of polyneuropathy. Velocity was most frequently abnormal, but only slightly more often than F wave latency and amplitude. We conclude that abnormality, as judged independently from two different types of evaluation, provides a sensitive and reliable minimal criterion for the diagnosis of neuropathy. Although symptoms, neurological deficits and abnormalities of nerve conduction are statistically associated, they should be evaluated separately to provide adequate characterization.
Suppression of tumourigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region. (1993)

Development of colon carcinomas appears to be associated with inactivation of multiple tumour suppressor genes. Cytogenetic and DNA analyses of colon carcinomas have detected a high frequency of chromosome 1p deletion, which suggests the presence of a tumour suppressor gene. We therefore introduced normal human chromosome 1 into colon carcinoma COKFu cells, through microcell hybridization. Six clones of hybrid cells containing normal chromosome 1 were obtained, four of which had a small fragment of the introduced chromosome 1, including 1p36-34. The morphology of hybrid cells with chromosome 1 markedly altered to a flat shape. The cloning efficiency of all six hybrid cells in soft agar was significantly reduced, and the tumourigenicity in athymic nude mice was completely suppressed. Hybrid cells containing only the region of 1p36-34, as well as those containing intact chromosome 1, showed suppressed transformed phenotype. Furthermore, several tumourigenic revertant cells were obtained from the hybrid cells. These revertant cells had a morphology similar to that of COKFu cells, and were found to have lost the 1p36 region from the introduced chromosome 1. These results indicate that a normal chromosome 1p36 carries a tumour suppressor gene for colon carcinogenesis.
Mutations at Sites Involved in Suc1 Binding Inactivate Cdc2 (1991)

suc1+ encodes an essential cell cycle regulator of the fission yeast Schizosaccharomyces pombe. Its product, a 13-kDa protein, interacts with the Cdc2 protein kinase. Both positive and negative effects on cell cycle progression have been attributed to Suc1. To date, the exact mechanisms and the physiological role of the interaction between Suc1 and Cdc2 remain unclear. Here we have studied the molecular basis of this association. We show that Cdc2 can bind Suc1 or its mammalian homolog directly in the absence of any additional protein component. Using an alanine scanning mutagenesis method, we analyzed the interaction between Cdc2 and Suc1. We show that the integrity of several domains on the Cdc2 protein, including sites directly involved in catalytic activity, is required for binding to Suc1. Furthermore, Cdc2 mutant proteins unable to bind Suc1 (but able to bind cyclins) are nonfunctional when overexpressed in S. pombe, indicating that a specific interaction with Suc1 is required for Cdc2 function.
MeD-Lights (2010)

Electronic health records (EHR) are poised to replace paper- based medical health records--EHRs show the promise of improving medical care by providing immediate access to a patient's records without having to worry about human-introduced delays. At the same time, mobile devices such as smartphones enable users to maintain their own medical information such as personal health records (PHR) as well as control the dissemination and sharing of their EHRs with medical personnel. Deciding what records to share with which medical personnel, however, is complicated by the many different types of records and users' varying privacy preferences. Thus, a usable model is needed to allow users to control the sharing of EHRs.
Structured space-time block codes with optimal diversity-multiplexing tradeoff and minimum delay (2004)

It is well-known that using multiple antennas can substantially increase the data rate and robustness of communication systems in a fading environment. It was recently established that there is a tradeoff between these two types of gains, termed diversity-multiplexing tradeoff. We develop a family of short structured space-time block codes that achieves the optimal tradeoff for the two-transmit two-receive antenna system with the minimum delay of two necessary for optimality. It uses the idea of rotation of cross-diagonal entries of an uncoded system to achieve spreading of information across space and time to obtain the maximum diversity while preserving multiplexing gain. Rotation angles that are optimal in terms of a determinant criterion and universal for all rates are identified. Performance analysis and simulation results are presented to demonstrate the achieved tradeoff.
Evolving trends in the long-term treatment of bipolar disorder (2006)

The episodic and chronic nature of bipolar disorder usually requires long-term treatment in all patients, yet there is an unmet need for well-tolerated and clinically effective maintenance therapy with enhanced patient adherence. Few well-tolerated treatment options are currently available that are both effective in all phases of bipolar disorder and prevent recurrence of episodes. Lithium has well-established efficacy in the prevention of further manic episodes and may also be effective in the prevention of depression and suicide, but safety is a concern due to narrow therapeutic window. For valproate and carbamazepine, data appear much less compelling. Lamotrigine has shown to be effective for long-term prevention of depressive episodes. Controlled studies suggest that atypical antipsychotics may also have mood-stabilizing properties and might become standard for long-term therapy in the new future. The role of psychoeducation in improving adherence to medication in long-term treatment and overall patient outcomes is also crucial.
Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. (1993)

Myeloid cell activation by lipopolysaccharides (LPS) involves two proteins, plasma LPS-binding protein (LBP) and cell-membrane CD14. Cell membrane CD14, anchored by a glycerophosphatidylinositol tail, is the cellular receptor for LPS-LBP complexes. Another form of CD14, without the lipid tail, circulates as a soluble plasma protein. In this work we show that soluble CD14 (sCD14) is required for activation of endothelial and epithelial cells by LPS. We propose that LPS-LBP complexes transfer LPS to sCD14, and the LPS-sCD14 complexes then bind to a cellular receptor. Support for this pathway comes from experiments in which LBP and CD14 in normal human serum are blocked by specific antibodies, experiments in which serum is replaced by purified LBP and sCD14, and experiments in which specific binding of [3H]LPS to epithelial cells is quantitated.
Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase Inhibitor (2008)

The efficient total synthesis of the recently described natural substance largazole (1) and its active metabolite largazole thiol (2) is described. The synthesis required eight linear steps and proceeded in 37% overall yield. It is demonstrated that largazole is a pro-drug that is activated by removal of the octanoyl residue from the 3-hydroxy-7-mercaptohept-4-enoic acid moiety to generate the active metabolite 2, which is an extraordinarily potent Class I histone deacetylase inhibitor. Synthetic largazole and 2 have been evaluated side-by-side with FK228 and SAHA for inhibition of HDACs 1, 2, 3, and 6. Largazole and largazole thiol were further assayed for cytotoxic activity against a panel of chemoresistant melanoma cell lines, and it was found that largazole is substantially more cytotoxic than largazole thiol; this difference is attributed to differences in the cell permeability of the two substances.
Cognitive Effects of Levetiracetam versus Topiramate (2008)

The Influence of Antiepileptic Drugs on Cognition: A Comparison of Levetiracetam with Topiramate. Gomer B, Wagner K, Frings L, Saar J, Carius A, Härle M, Steinhoff BJ, Schulze-Bonhage A. Epilepsy Behav 2007;10(3):486–494. Levetiracetam (LEV) and topiramate (TPM) are considered highly effective novel antiepileptic drugs (AEDs) in the treatment of focal epilepsies. To explore potential side effects, this study investigated their influence on cognitive functions comparatively by means of a standardized neuropsychological test battery assessing several cognitive domains. In this observational study, cognitive changes were explored in 30 consecutively recruited patients with focal epilepsy treated with LEV and in 21 patients treated with TPM, comparing functions assessed prior to gradual initiation and after reaching steady state of the individual target dosage. Before titration, patient groups did not differ significantly with respect to cognitive performance. Whereas the LEV group manifested no change in cognitive performance after AED titration, the TPM group worsened in the cognitive domains of cognitive speed and verbal fluency, as well as short-term memory. These findings suggest that TPM, unlike LEV, may impair frontal lobe functions. The lack of cognitive side effects related to LEV treatment may be relevant for treatment decisions.
A 15–40 GHz CMOS True-Time Delay Circuit for UWB Multi-Antenna Systems (2013)

A CMOS true-time delay (TTD) circuit operating from 15 to 40 GHz is presented for integrated UWB multi-antenna systems. The TTD circuit employs a distributed active switching structure in which eight cascode switches are distributed along transmission lines, leading to 3-bit variations of the group delay. The size of the switches and the characteristic impedance of the transmission lines are carefully scaled so as to minimize loss variation among the different delay states, while maintaining flat delay performance over a wide bandwidth. The circuit is implemented in a bulk 0.13-μm CMOS technology and exhibits a total variable group delay of 40 ps with an average resolution of 5 ps from 15 to 40 GHz. The insertion loss was 14 dB with a maximum RMS variation of 1.6 dB, while the input and output return loss was better than 10 dB over the operating bandwidth.
RTP Payload Format for MPEG-4 Audio/Visual Streams (2011)

This document describes Real-Time Transport Protocol (RTP) payload
formats for carrying each of MPEG-4 Audio and MPEG-4 Visual bitstreams
without using MPEG-4 Systems. For the purpose of directly mapping
MPEG-4 Audio/Visual bitstreams onto RTP packets, it provides
specifications for the use of RTP header fields and also specifies
fragmentation rules. It also provides specifications for Media Type
registration and the use of Session Description Protocol (SDP). The
audio payload format described in this document has some limitations
related to the signaling of audio codec parameters for the required
multiplexing format. Therefore, for new system designs RFC 3640 is
preferred, which does not have these restrictions. This document
obsoletes RFC 3016. A revision of RFC 3016 was required because of
some misalignments between RFC 3016 and the 3GPP PSS specification
regarding the RTP payload format for MPEG-4 Audio. Changes from RFC
3016 are summarized in Section 11. Issues on backward compatibility to
RFC 3016 are discussed in Section 1.3.
TNF Type 2 Receptor (p75) Lowers the Threshold of T Cell Activation (2001)

Abstract T cell activation requires a threshold amount of TCR-mediated signals, an amount that is reduced by signals mediated through costimulatory molecules expressed on the T cell surface. Here the role of TNFR2 (p75) as a putative costimulatory receptor for T cell activation was examined. It was found that p75 deficiency in CD8+ T cells increased the requirements for TCR agonist approximately 5-fold. Furthermore, p75−/− T cells display a marked reduction in the proliferative response to TCR agonist. This hypoproliferative response was associated with delayed kinetics of induction of the acute activation markers CD25 and CD69 as well as a marked decrease in the production of IL-2 and IFN-γ. The net result is that very few cells are recruited into the dividing population. Interestingly, CD28 costimulation was only partially effective in rescuing the proliferative defect of p75−/−CD8+ T cells. Thus, p75 provides an important costimulatory signal in addition to that provided by CD28 toward optimal T cell proliferation.
Substrate and inhibitor studies on proteinase 3 (1992)

Various amino acid and peptide thioesters were tested as substrates for human proteinase 3 and the best substrate is Boc-Ala-Ala-Nva-SBzl with a kcat/Km value of 1.0 x 10(6) M-1.s-1. Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with kcat/Km values of (1-4) x 10(5) M-1.s-1. Substituted isocoumarins are potent inhibitors of proteinase 3 and the best inhibitors are 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarin and 3,4-dichloroisocoumarin (DCI) with kobs/[I] values of 4700 and 2600 M-1.s-1, respectively. Substituted isocoumarins, peptide phosphonates and chloromethyl ketones inhibited proteinase 3 less potently than human neutrophil elastase (HNE) by 1-2 orders of magnitude.
Correcting spurious resolution in defocused images (2007)

Optical modeling suggests that levels of retinal defocus routinely caused by presbyopia should produce phase reversals (spurious resolution-SR) for spatial frequencies in the 2 cycles/letter range known to be critical for reading. Simulations show that such reversals can have a decisive impact on character legibility, and that correcting only this feature of defocused images (by re-reversing contrast sign errors created by defocus) can make unrecognizably blurred letters completely legible. This deblurring impact of SR correction is remarkably unaffected by the magnitude of defocus, as determined by blur-circle size. Both the deblurrring itself and its robustness can be understood from the effect that SR correction has on the defocused pointspread function, which changes from a broad flat cake to a sharply pointed cone. This SR-corrected pointspread acts like a delta function, preserving image shape during convolution regardless of blur-disk size. Curiously, such pointspread functions always contain a narrow annulus of negative light-intensity values whose radius equals the diameter of the blur circle. We show that these properties of SR-correction all stem from the mathematical nature of the Fourier transform of the sign of the optical transfer function, which also accounts for the inevitable low contrast of images pre-corrected for SR.
Set theoretic inverse halftoning (2002)

We give a general method to recover a continuous-tone image from a halftone image in the situation where the halftoning algorithm is known. Using rigorous mathematical tools, the method combines what we call the visual information and the coding information of the halftone data. Although we concentrate on halftoning by error diffusion, the method is applicable to all digital halftoning techniques.
ATM&amp;A Key Determinant of Multiple Cellular Responses to Irradiation (2001)

Ataxia-telangiectasia is a rare clinical disorder manifesting a variety of different abnormalities, including progressive neurodegeneration, increased cancer incidence, immune deficiency, sterility, and extreme radiosensitivity. Recent studies have demonstrated that the defective gene product in this disease, ATM, is a protein kinase. The identification of several different substrates for this kinase is beginning to explain the wide array of different physiologic abnormalities that occur when this gene product is dysfunctional. Since the ATM protein is a critical signaling molecule in the cellular response to ionizing irradiation, the identification of these substrates also results in elucidation of the steps involved in a number of different cellular signaling pathways initiated by irradiation. Such insights also result in the identification of potential new targets for enhancing the efficacy of radiation therapy.
Resource management in action on the ward. (1990)

The implementation of resource management at the Radcliffe Infirmary made clinical managers responsible for their ward budgets. This article describes how a nursing system was developed to facilitate the planning and management of resources at ward level.
Synthesis of a Dibromoperylene Phosphoramidite Building Block and Its Incorporation at the 5′ End of a G-Quadruplex Forming Oligonucleotide: Spectroscopic Properties and Structural Studies of the Resulting Dibromoperylene Conjugate (2011)

Previous studies indicate that some perylene bisimide derivatives can drive the assembly of DNA G-quadruplexes, thus suggesting the possible advantage in the adoption of perylene-conjugated G-rich oligonucleotides in biological and biotechnological applications. Nevertheless, the typical poor solubility of perylene bisimides strongly limits the number of suitable chemical strategies to prepare perylene-conjugated oligonucleotides. In order to overcome these difficulties, we employed the earlier described core twisted perylene derivatives possessing unique optical and electronic properties, besides good solubility in common solvents. As a first result, the large-scale synthesis of a new dibromoperylene derivative (PEOEBr) phosphoramidite building block is herein reported. Furthermore, the structural behavior of the conjugated PEOEBr-GGGTTAGGG (HTRp2) human telomeric repeat was investigated by using CD, UV, fluorescence, and gel electrophoresis techniques in desalted water and in K(+)- and Na(+)-containing buffers. We observed that the peculiar property of PEOEBr moieties to form dimers instead of extended aggregates drives the HTRp2 strands toward dimerization and mainly promotes the formation of quadruplex species having both the 5'-ends located at the same side of the structures. However, the counterions present in solutions (K(+) or Na(+)) as well as the strand concentration, also contribute to influence the topology and the stoichiometry of formed structures. Furthermore, unlike the unmodified sequence GGGTTAGGG (HTR2), HTRp2 strands quickly associate into G-quadruplexes even in desalted water, as assessed by CD experiments.
Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages (2004)

Organs developing as appendages of the ectoderm are initiated from epithelial thickenings called placodes. Their formation is regulated by interactions between the ectoderm and underlying mesenchyme, and several signalling molecules have been implicated as activators or inhibitors of placode formation. Ectodysplasin (Eda) is a unique signalling molecule in the tumour necrosis factor family that, together with its receptor Edar, is necessary for normal development of ectodermal organs both in humans and mice. We have shown previously that overexpression of the Eda-A1 isoform in transgenic mice stimulates the formation of several ectodermal organs. In the present study, we have analysed the formation and morphology of placodes using in vivo and in vitro models in which both the timing and amount of Eda-A1 applied could be varied. The hair and tooth placodes of K14-Eda-A1 transgenic embryos were enlarged, and extra placodes developed from the dental lamina and mammary line. Exposure of embryonic skin to Eda-A1 recombinant protein in vitro stimulated the growth and fusion of placodes. However, it did not accelerate the initiation of the first wave of hair follicles giving rise to the guard hairs. Hence, the function of Eda-A1 appears to be downstream of the primary inductive signal required for placode initiation during skin patterning. Analysis of BrdU incorporation indicated that the formation of the epithelial thickening in early placodes does not involve increased cell proliferation and also that the positive effect of Eda-A1 on placode expansion is not a result of increased cell proliferation. Taken together, our results suggest that Eda-A1 signalling promotes placodal cell fate during early development of ectodermal organs.
An Improved Method for the Mono-Hydroxymethylation of Pyridines. A Modification of the Minisci Procedure (1989)

Abstract The reaction of N-methoxy-derivatives of pyridines in methanol with ammonium persulphate gives improved yields of mono-hydroxymethylated products. In contrast to the original Minisci procedure the reaction requires only catalytic amounts of ammonium persulphate. Evidence is presented which establishes that the reaction does not proceed via an intramolecular pathway.
Physical mapping of herpes simplex virus-induced polypeptides (1978)

Analysis of the polypeptides induced by 29 herpes simplex virus type 1/type 2 intertypic recombinants and correlation of the data with the crossover points in the recombinant DNAs have enabled the map positions of many polypeptides to be deduced. These include 25 polypeptides which label with [35S]methionine, 11 which label with [32P]orthophosphate, and 4 which label with [14C]glucosamine. Together with the data of Preston et al. (J. Virol., in press) on the mapping of five immediate-early polypeptides, the results show that representatives of four groups of proteins--immediate-early, late, phosphorylated, and glycosylated--map in both long and short regions. The functional organization of the herpes simplex virus genome does not therefore restrict any of these four groups to either the long or the short region.
Hydrodynamics of Diamond-Shaped Gradient Nanopillar Arrays for Effective DNA Translocation into Nanochannels (2015)

Effective DNA translocation into nanochannels is critical for advancing genome mapping and future single-molecule DNA sequencing technologies. We present the design and hydrodynamic study of a diamond-shaped gradient pillar array connected to nanochannels for enhancing the success of DNA translocation events. Single-molecule fluorescence imaging is utilized to interrogate the hydrodynamic interactions of the DNA with this unique structure, evaluate key DNA translocation parameters, including speed, extension, and translocation time, and provide a detailed mapping of the translocation events in nanopillar arrays coupled with 10 and 50 μm long channels. Our analysis reveals the important roles of diamond-shaped nanopillars in guiding DNA into as small as 30 nm channels with minimized clogging, stretching DNA to nearly 100% of their dyed contour length, inducing location-specific straddling of DNA at nanopillar interfaces, and modulating DNA speeds by pillar geometries. Importantly, all critical features down to 30 nm wide nanochannels are defined using standard photolithography and fabrication processes, a feat aligned with the requirement of high-volume, low-cost production.