gebhart/patrepeval huggingface dataset:
Repulsive Guidance Molecule (RGMa), a DRAGON Homologue, Is a Bone Morphogenetic Protein Co-receptor (2005)

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGF-beta) superfamily of ligands, which regulate many mammalian physiologic and pathophysiologic processes. BMPs exert their effects through type I and type II serine/threonine kinase receptors and the Smad intracellular signaling pathway. Recently, the glycosylphosphatidylinositol (GPI)-anchored protein DRAGON was identified as a co-receptor for BMP signaling. Here, we investigate whether a homologue of DRAGON, repulsive guidance molecule (RGMa), is similarly involved in the BMP signaling pathway. We show that RGMa enhances BMP, but not TGF-beta, signals in a ligand-dependent manner in cell culture. The soluble extracellular domain of RGMa fused to human Fc (RGMa.Fc) forms a complex with BMP type I receptors and binds directly and selectively to radiolabeled BMP-2 and BMP-4. RGMa mediates BMP signaling through the classical BMP signaling pathway involving Smad1, 5, and 8, and it up-regulates endogenous inhibitor of differentiation (Id1) protein, an important downstream target of BMP signals. Finally, we demonstrate that BMP signaling occurs in neurons that express RGMa in vivo. These data are consistent with a role for RGMa as a BMP co-receptor.
Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice. (1994)

The physiological role of insulin-like growth factor (IGF) II (IGF-II) in adult humans is poorly understood. Rather high levels of IGF-II persist in adult human serum, whereas, in rodents, IGF-II levels are very low. To investigate the physiological and carcinogenic effects of persistently elevated IGF-II in adults, we have produced two lines of transgenic mice in which high levels of IGF-II (20- or 30-fold increase above normal) are persistently maintained in the blood. The transgene is driven by the major urinary protein promoter, and it is highly expressed in the liver and perputial glands in both lines. The adult transgenic mice are smaller than controls, and their body composition is altered. Their lean body mass is reduced by 5-8%, whereas fat mass is reduced between 44 and 77%. The mice expressing the highest level of IGF-II (30x) develop hypoglycemia and hypoinsulinemia and IGF-I levels are normal. Mice in the lower expression line (20-fold elevated IGF-II) develop hypoglycemia progressively over their lifetime. Mice from both lines also develop a diverse spectrum of tumors at a higher frequency than controls after 18 months of age, and the most frequent types of tumors are hepatocellular carcinomas and lymphomas. Squamous cell carcinoma, sarcoma, and thyroid carcinomas also occurred in our test group. The long latent period before tumors arise and the wide spectrum of tumor types suggest that IGF-II may function primarily as a tumor progression factor in mice via autocrine and endocrine mechanisms of action.
Spontaneous mutation in the Escherichia coli lacI gene. (1991)

To gain more detailed insight into the nature and mechanisms of spontaneous mutations, we undertook a DNA sequence analysis of a large collection of spontaneous mutations in the N-terminal region of the Escherichia coli lacI gene. This region of circa 210 base pairs is the target for dominant lacI mutations (i-d) and is suitable for studies of mutational specificity since it contains a relatively high density of detectable mutable sites. Among 414 independent i-d mutants, 70.8% were base substitutions, 17.2% deletions, 7.7% additions and 4.3% single-base frameshifts. The base substitutions were both transitions (60%) and transversions (40%), the largest single group being G.C----A.T (47% of base substitutions). All four transversions were observed. Among the 71 deletions, a hotspot (37 mutants) was present: an 87-bp deletion presumably directed by an 8-bp repeated sequence at its endpoints. The remaining 34 deletions were distributed among 29 different mutations, either flanked (13/34) or not flanked (21/34) by repeated sequences. The 32 additions comprised 29 different events, with only two containing a direct repeat at the endpoints. The single-base frameshifts were the loss of a single base from either repeated (67%) or nonrepeated (33%) bases. A comparison with the spectrum obtained previously in strains defective in DNA mismatch correction (mutH, mutL, mutS strains) yielded information about the apparent efficiency of mismatch repair. The overall effect was 260-fold but varied substantially among different classes of mutations. An interesting asymmetry was uncovered for the two types of transitions, A.T----G.C and G.C----A.T being reduced by mismatch repair 1340- and 190-fold, respectively. Explanations for this asymmetry and its possible implications for the origins of spontaneous mutations are discussed.
Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review (2020)

Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.
Coordination of Early Protective Immunity to Viral Infection by Regulatory T Cells (2008)

Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to local viral infection by allowing a timely entry of immune cells into infected tissue.
Dehydroepiandrosterone sulfate: kinetics of metabolism in normal young men and women. (1984)

The constant infusion technique was used to study the kinetics of dehydroepiandrosterone sulfate (DHEAS) metabolism in normal young men and women. The metabolic clearance rates (MCR) (means +/- SEM) for normal young men and women were 15.2 +/- 1.7 1/24 h (8.2 +/- 0.7 1/m2/24 h) and 11.8 +/- 0.8 1/24 h (7.3 +/- 0.4 1/m2/24 h) respectively. Coupled with the plasma levels of 5.07 +/- 1.95 and 4.02 +/- 0.57 mumole/L the resulting blood production rates were 76.7 +/- 25.7 and 48.0 +/- 9.4 mumole/24 h for men and women respectively. The conversion ratios for the conversion of DHEAS to dehydroepiandrosterone (DHEA) were 0.006 for men and 0.004 for women. Because of the high metabolic clearance rates for DHEA relative to those for DHEAS and the high production rates of DHEAS most of the DHEA produced per day can arise from DHEAS.
The conserved B3 domain of VIVIPAROUS1 has a cooperative DNA binding activity. (1997)

The biochemical activities that underlie the genetically defined activator and repressor functions of the VIVIPAROUS1 (VP1) protein have resisted in vitro analysis. Here, we show that a glutathione S-transferase (GST) fusion protein, including only the highly conserved B3 domain of VP1, has a highly cooperative, sequence-specific DNA binding activity. GST fusion proteins that include larger regions of the VP1 protein have very low activity, indicating that removal of the flanking protein sequences is necessary to elicit DNA binding in vitro. DNA competition and DNase I footprinting analyses show that B3 binds specifically to the Sph element involved in VP1 activation of the C1 gene, whereas binding to the G-box-type VP1-responsive element is of low affinity and is nonspecific. Footprint analysis of the C1 promoter revealed that sequences flanking the core TCCATGCAT motif of Sph also contribute to the recognition of the Sph element in its native context. The salient features of the in vitro GST-B3 DNA interaction are in good agreement with the protein and DNA sequence requirements defined by the functional analyses of VP1 and VP1-responsive elements in maize cells.
The Emergence of Drug-Resistant Tuberculosis in New York City (1993)

There has been a marked increase in drug-resistant tuberculosis in New York City. Previously treated patients, those infected with HIV, and injection-drug users are at increased risk for drug resistance. Measures to control and prevent drug-resistant tuberculosis are urgently needed.
Phenelzine and Amitriptyline in the Treatment of Depression (1980)

We present the results of a direct comparison of pheneizine sulfate and amitriptyline hydrochloride therapy in 105 depressed patients. We believe this is the first definitive double-blind controlled clinical trial of a monoamine oxidase inhibitor and a tricyclic antidepressant in the outpatient setting. The results show both antidepressants to be effective, with the similarities between the two exceeding the differences. Both drugs had marked antidepressant and antianziety effects. Phenelzine tended to exert a stronger antianxiety action; amitriptyline was more effective in reversing weight loss and improving sleep. The incidence of two side effects, sedation and orthostatic hypotension, was almost identical. Dry mouth was more prevalent with amitriptyline. We discuss the indications for the differential clinical use of both drugs in depressed outpatients.
Synthesis of UnprotectedO-Glycosyl Trichloroacetimidates and Their Reactivity Towards some Glycosyl Acceptors1 (1993)

The preparation of O-unprotected sugars which are activated at the anomeric position with a trichloroacetimidate group is described. Furthermore, some examples illustrate the reactivity of these derivatives as glycosyl donors. They react with different glycosyl acceptors in the presence of an acid catalyst; the yields and the α/β-stereoselectivities depend highly on the reaction conditions.
Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations (2012)

The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged ≥ 25 y and women ≥ 50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and controls (SF >100 µg/L in men, SF >50 µg/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7 × 10(-6)) and replicated in African Americans (p = 0.0012).Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p<4.4 × 10(-5)); six SNPs replicated in other ethnicities (p<0.01). SNP rs10904850 in the CUBN gene on 10p13 was associated with serum iron in African Americans (P = 1.0 × 10(-5)). These results confirm known associations with iron measures and give unique evidence of their role in different ethnicities, suggesting origins in a common founder.
NOy Blue Ribbon panel (1996)

Total NO y was determined on the Pacific Exploratory Mission‐West A using two separate instruments, one operated by Georgia Institute of Technology and one by Nagoya University. The two data sets exhibited significant disagreement, with no systematic correlation, and differences often a factor of 2 or more. Additionally, regardless of data set chosen, the total NO y was much greater than the sum of its components measured separately. A panel was convened by NASA in July 1993 to examine these conflicting datasets and the question of “missing NO y ” on this mision. This paper reports the conclusions and recommendations from the panel.
Runtime asynchronous fault tolerance via speculation (2012)

Transient faults are emerging as a critical reliability concern in modern microprocessors. Redundant hardware solutions are commonly deployed to detect transient faults, but they are less flexible and cost-effective than software solutions. However, software solutions are rendered impractical because of high performance overheads. To address this problem, this paper presents Runtime Asynchronous Fault Tolerance via Speculation (RAFT), the fastest transient fault detection technique known to date. Serving as a layer between the application and the underlying platform, RAFT automatically generates two symmetric program instances from a program binary. It detects transient faults in a non-invasive way and exploits high-confidence value speculation to achieve low runtime overhead. Evaluation on a commodity multicore system demonstrates that RAFT delivers a geomean performance overhead of 2.83% on a set of 30 SPEC CPU benchmarks and STAMP benchmarks. Compared with existing transient fault detection techniques, RAFT exhibits the best performance and fault coverage, without requiring any change to the hardware or the software applications.
Peptide Phage Display as a Tool for Drug Discovery: Targeting Membrane Receptors (2011)

Ligands selected from phage-displayed random peptide libraries tend to be directed to biologically relevant sites on the surface of the target protein. Consequently, peptides derived from library screenings often modulate the target protein's activity in vitro and in vivo and can be used as lead compounds in drug design and as alternatives to antibodies for target validation in both genomics and drug discovery. This review discusses the use of phage display to identify membrane receptor modulators with agonistic or antagonistic activities. Because isolating or producing recombinant membrane proteins for use as target molecules in library screening is often impossible, innovative selection strategies such as panning against whole cells or tissues, recombinant receptor ectodomains, or neutralizing antibodies to endogenous binding partners were devised. Prominent examples from a two-decade history of peptide phage display will be presented, focusing on the design of affinity selection experiments, methods for improving the initial hits, and applications of the identified peptides.
Eurotra: A European perspective on MT (1986)

This paper describes the perspective on Machine Translation taken in the Eurotra project: an R & D project of the European Communities at a relatively early stage. It describes: i) the project's rather challenging aims; ii) the framework of design principles and linguistic and software methodology which are of particular importance given its size, scope, and organization; iii) the proposed representational theories and expressive (programming) languages with which actual instances of MT systems can be constructed. The final section sketches some recent proposals and directions for future research.
An extended range‐modified gradient technique for profile inversion (1993)

A method for reconstructing the complex index of refraction of a bounded inhomogeneous object from measured scattered field data is presented. The index and the unknown fields within the object are simultaneously reconstructed in an iterative algorithm. The method is a refinement of earlier work which incorporates a more effective way to update the unknowns at each stage of the iteration. Considerable efficiency in the algorithm is achieved. Some numerical examples are given indicating the limits on the contrasts which can be reconstructed. These limits show that the range of contrasts that may be reconstructed is extended over that achievable with the earlier work.
Identification of highly potent and selective Tyk2 inhibitors for the treatment of autoimmune diseases through structure-based drug design (THER2P.961) (2015)

Abstract The JAK family kinase Tyk2 is essential for IL-12 and IL-23 signaling, which are associated with Th1 and Th17 cell differentiation and activation. The Th1 and Th17 pathways have been implicated in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD) thereby making Tyk2 a highly attractive target for the treatment of these disorders. However, given the high degree of sequence homology between the JAK family kinases, designing potent and selective Tyk2 inhibitors remains a challenge. Using an innovative structure-based approach, we have designed, synthesized and characterized small molecule inhibitors optimized for JAK family selectivity using computational free energy perturbation (FEP) methods and medicinal chemistry SAR. We have identified selective Tyk2 inhibitors with pM activity against Tyk2 (Ki=140-520 pM) and &amp;gt;100 fold selectivity over JAK2 and JAK1 with more moderate selectivity over JAK3. These analogs are orally bioavailable (85%F) with suitable drug-like properties. NDI-031232 was determined to be highly selective across 359 kinases, and is a potent inhibitor of IL-12 induced pSTAT4 in hPBMCs (IC50=17 nM) and IL-12 induced IFNg in human whole blood (IC50=520 nM). NDI-031232 also demonstrated robust efficacy in blocking IL-12-mediated IFNg production in an ex vivo mouse model. Therefore, selective inhibitors of Tyk2 retain the anti-inflammatory activity while reducing potential for dose-limiting side effects observed with non-selective JAK inhibitors.
Performance of ultra-wideband communications with suboptimal receivers in multipath channels (2002)

The performance of a single-user ultra-wideband (UWB) communication system employing binary block-coded pulse-position modulation (PPM) and suboptimal receivers in multipath channels is considered. The receivers examined include a RAKE receiver with various diversity combining schemes and an autocorrelation receiver, which is used in conjunction with transmitted reference (TR) signaling. A general framework is provided for deriving the performance of these receivers in multipath channels corrupted by additive white Gaussian noise (AWGN). By employing previous measurements of indoor UWB channels, we obtain numerical results for several cases which illustrate the tradeoff between performance and receiver complexity.
Recent Patents and Advances in the Next-Generation Sequencing Technologies (2008)

We are now witnessing a new genomic revolution due to the arrival and continued advancements in the next-generation high-throughput sequencing technologies, which encompass sequencing by synthesis including fluorescent in situ sequencing (FISSEQ) and pyrosequencing, sequencing by ligation including using polony amplification and supported oligonucleotide detection (SOLiD), sequencing by hybridization in combination with sequencing-by-ligation and nanopore technology, nanopore sequencing and other novel sequencing technologies using nano-transistor array, scanning tunneling microscopy and nanowire molecule sensors etc. We review here major technologies and recent patents for achieving high-throughput, ultra-fast, extremely cheap, and highly accurate sequencing. We will see enormous impacts of these next-generation sequencing methods for solving complex biological problems and for ushering in the practice of personalized medicine.
CORRELATION BETWEEN ELECTRICAL AND STRUCTURAL PROPERTIES OF FLUORAPATITES (1999)

Materials with the apatitic structure M10(XO4)Y2 possess unique properties as catalysts, sensor, ionic exchangers and biomaterials. The physico-chemical properties of these materials depend hardly on the ions nature, on that of charge carrier and on their localisation in the hote sites. The apatite materials have a great stability and a good capacity of change and substitutions, so their electrical properties may be modulated by just variation of their chemical composition. The electrical properties study using complex impedance method at high temperature allows to demonstrate an anonic conductivity for M10(PO4)6F2 (M=Ca, Sr, Pb, Ba) and a mixed ionic conductivity for Ca10-xM'x(PO4)6-x(SO4)xF2 (M'=Na, Li). The size ion, the charge and the polarisability of cation introduced in matrix are responsibles of mechanism conductivity. Those results allow to appreciate the correlation between electrical and structural properties.
InstaBoost: Boosting Instance Segmentation via Probability Map Guided Copy-Pasting (2019)

Instance segmentation requires a large number of training samples to achieve satisfactory performance and benefits from proper data augmentation. To enlarge the training set and increase the diversity, previous methods have investigated using data annotation from other domain (e.g. bbox, point) in a weakly supervised mechanism. In this paper, we present a simple, efficient and effective method to augment the training set using the existing instance mask annotations. Exploiting the pixel redundancy of the background, we are able to improve the performance of Mask R-CNN for 1.7 mAP on COCO dataset and 3.3 mAP on Pascal VOC dataset by simply introducing random jittering to objects. Furthermore, we propose a location probability map based approach to explore the feasible locations that objects can be placed based on local appearance similarity. With the guidance of such map, we boost the performance of R101-Mask R-CNN on instance segmentation from 35.7 mAP to 37.9 mAP without modifying the backbone or network structure. Our method is simple to implement and does not increase the computational complexity. It can be integrated into the training pipeline of any instance segmentation model without affecting the training and inference efficiency. Our code and models have been released at https://github.com/GothicAi/InstaBoost
A conditional keeper technique for sub-0.13μ wide dynamic gates (2002)

Increasing leakage currents seriously limits the robustness of wide dynamic gates. We present an efficient, conditional keeper technique, where a large fraction of the keeper is turned ON only if the dynamic output remains high in the evaluation phase. Thus, strong keepers can be utilized with leaky gates without significant impact on performance of the gates. Compared to the conventional technique, 9-to-35% higher performances have been observed across 8-to-32-bit wide dynamic gates in a 0.13 /spl mu/m technology.