gebhart/patrepeval huggingface dataset:
Epithelial‐mesenchymal interactions in the alteration of gene expression and morphology following lung injury (1997)

Numerous studies using morphologic techniques have demonstrated the plasticity of pulmonary epithelial cells and the requirement for complex intercellular interactions for regeneration of normal epithelium following lung injury. Recent developments in the molecular characterization of genes expressed in the lung have generated additional tools for evaluation of lung cell phenotypes and interactions. This review discusses the relationship between molecular and morphologic changes in lung cells during injury and repair. Changes in epithelial morphology and their differentiated gene products may be mediated through alterations in expression of numerous factors acting through paracrine and autocrine mechanisms. Tumor necrosis factor alpha, transforming growth factor beta, and retinoic acid, whose roles in the regulation of epithelial cell differentiation have been well documented, will be discussed in the context of normal lung development and repair from injury. Microsc. Res. Tech. 38:473–479, 1997. © 1997 Wiley-Liss, Inc.
Spectroscopic characterization of thioredoxin covalently modified with monofunctional organoarsenical reagents (1987)

Thioredoxin upon reduction with mercaptoethylamine was subjected to covalent modification by the monofunctional organoarsenical reagents H2NPhAsO and HO(CH2)4AsCl2. The degree of modification was monitored by the percentage loss in free thiol content as measured by the reaction with the thiol reagent 5,5'-dithiobis(2-nitrobenzoic acid). The modification results in the formation of a stable 15-membered cyclic dithioarsenite ring that readily extrudes the arsenic moiety upon the addition of 2,3-dimercaptopropanol. The conformational effects of this modification were monitored by steady-state fluorescence and circular dichroism. On the basis of circular dichroic spectra, it appeared that the protein experiences no significant backbone conformational change from this modification. The degree of conformational change was found to be within the range observed upon reduction of the oxidized thioredoxin. Steady-state fluorescence revealed that the arsenicals caused strong quenching of the tryptophan fluorescence. Stern-Volmer titrations revealed that the quenching was a function of both the nature of the organic group and its covalent attachment to the "spatially close" thiols. The analysis of the spectroscopic results obtained with the arsenical reagents provides further insight into the nature of the conformational change that has been observed upon reduction of thioredoxin.
Network Sketching: Exploiting Binary Structure in Deep CNNs (2017)

Convolutional neural networks (CNNs) with deep architectures have substantially advanced the state-of-the-art in computer vision tasks. However, deep networks are typically resource-intensive and thus difficult to be deployed on mobile devices. Recently, CNNs with binary weights have shown compelling efficiency to the community, whereas the accuracy of such models is usually unsatisfactory in practice. In this paper, we introduce network sketching as a novel technique of pursuing binary-weight CNNs, targeting at more faithful inference and better trade-off for practical applications. Our basic idea is to exploit binary structure directly in pre-trained filter banks and produce binary-weight models via tensor expansion. The whole process can be treated as a coarse-to-fine model approximation, akin to the pencil drawing steps of outlining and shading. To further speedup the generated models, namely the sketches, we also propose an associative implementation of binary tensor convolutions. Experimental results demonstrate that a proper sketch of AlexNet (or ResNet) outperforms the existing binary-weight models by large margins on the ImageNet large scale classification task, while the committed memory for network parameters only exceeds a little.
Physical properties of oligonucleotides containing phosphoramidate-modified internucleoside linkages (1991)

Because of their nuclease resistance and ability to form substrates for RNase H, antisense oligodeoxynucleotides (ODNs) possessing several methoxyethylphosphoramidate linkages at both termini have proven effective at targeting the degradation of specific mRNAs in Xenopus embryos. The efficacy of these compounds subsequently observed in tissue culture focused our attention on the issue of cellular uptake. To investigate the extent to which phosphate backbone modifications may increase the lipophilicity of ODNs, and thereby increase passive uptake by cells, the partitioning of a series of phosphoramidate-modified compounds between aqueous and organic phases was examined. The octanol:water partition coefficient of an unmodified, mixed-sequence 16-mer was 1.75 x 10(-5). The log of the partition coefficient increased in a sigmoidal manner with the number of methoxyethylphosphoramidate internucleoside linkages, indicating a nonlinear free energy relationship. The highest level of partitioning demonstrated was approximately 4 x 10(-3) (a 230-fold increase), attained when 11 of the 15 phosphodiesters were modified. An increase in hydrophobicity was also attained with C8 and C10 alkylamines acting as phase-transfer agents. The melting temperatures of heteroduplexes formed between a phosphoramidate-modified ODN and a complementary unmodified DNA strand decreased by approximately 1.5 degrees C for every phosphate group modification. ODNs can thus be extensively derivatized without substantially compromising duplex formation under physiological conditions.
Clostridium difficile–related Hospitalizations among US Adults, 2006 (2008)

salons. M. conceptionense belongs to the M. fortuitum group and was isolated in a posttraumatic osteitis infl ammation (10). M. chimaera belongs to MAC and has been isolated only in patients with pulmonary disorders but not from immunocompromised patients. The authors reported that the isolate showed unusually high virulence. We isolated this species for the fi rst time in an environmental sample. It could belong to the transitory fl ora of the H cooling tower because it was isolated only once in our samples. Cooling towers already had been investigated for slow-growing mycobacteria (1), and our study showed they also can be an environmental source of rapidly growing NTM pathogens. In our procedure for amebal co-cultures, incubation cannot last >10 days because amebae do not survive longer in Page's amebal saline buffer. Moreover, agar plates were incubated for 10 days only, which explains why we could recover only rapidly growing mycobacteria. The cooling towers, already known as a source of dissemination of Legionella spp., may disseminate mycobacteria in aerosols and be a previously nonrecognized source of infection.
Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: Safety and clinical activity. (2016)

5533 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab in patients (pts) with recurrent/refractory ovarian cancer (OC; NCT01772004). Methods: Pts with advanced OC unselected for PD-L1 expression received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Unconfirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry. Results: As of Oct 23, 2015, 124 pts were treated with avelumab (median 12 wks [range 2-54]) and followed for a median of 54 wks (range 11-101). Median age was 62 y (range 27-84), ECOG PS was 0 (47.6%) or 1 (52.4%), and median number of prior therapies was 4 (range 1-13). Treatment-related (TR) AEs occurred in 82 pts (66.1%); most common (≥10%) were fatigue (13.7%), infusion-related reaction (12.1%), and diarrhea (11.3%), all of grade 1/2. Grade 3/4 TRAEs were reported in 8 pts (6.5%); of these, only increased lipase occurred in > 1 pt (n = 2). There were no treatment-related deaths. ORR was 9.7% (95% CI: 5.1-16.3) based on 12 partial responses; 6 were ongoing. Stable disease was observed in 55 pts (44.4%); disease control rate was 54.0%. PD-L1 expression was evaluable in 74 pts (59.7%). Using a ≥1% cutoff for tumor cell staining, 57/74 (77.0%) were PD-L1+ and ORR was 12.3% in PD-L1+ (7/57; 95% CI: 5.1, 23.7) vs 5.9% in PD-L1− pts (1/17; 95% CI: 0.1, 28.7). Overall, median PFS was 11.3 wks (95% CI: 6.1, 12.0) and median OS was 10.8 mos (95% CI: 7.0, 16.1). Conclusions: Single-agent avelumabshowed an acceptable safety profile and clinical activity in heavily pretreated pts with OC. These data represent the largest study of anti-PD(L)1 agents in pts with OC to date. The potential relationship between biomarkers, such as germline BRCA mutational status, and the probability of response is being investigated. Randomized phase 3 trials of avelumab in OC are underway. *Proposed INN. Clinical trial information: NCT01772004.
Isolation and characterization of a human cDNA for mRNA 5'-capping enzyme (1998)

The human mRNA 5'-capping enzyme cDNA was identified. Three highly related cDNAs, HCE1 (human mRNAcappingenzyme1), HCE1A and HCE1B , were isolated from a HeLa cDNA library. The HCE1 cDNA has the longest ORF, which can encode a 69 kDa protein. A short region of 69 bp in the 3'-half of the HCE1 ORF was missing in HCE1A and HCE1B , and, additionally, HCE1B has an early translation termination signal, which suggests that the latter two cDNAs represent alternatively spliced product. When expressed in Escherichia coli as a fusion protein with glutathione S -transferase, Hce1p displayed both mRNA 5'-triphosphatase (TPase) and mRNA 5'-guanylyltransferase (GTase) activities, and it formed a cap structure at the 5'-triphosphate end of RNA, demonstrating that it indeed specifies an active mRNA 5'-capping enzyme. The recombinant proteins derived from HCE1A and HCE1B possessed only TPase activity. When expressed from ADH1 promoter, HCE1 but not HCE1A and HCE1B complemented Saccharomyces cerevisiae CEG1 and CET1 , the genes for GTase and TPase, respectively. These results demonstrate that the N-terminal part of Hce1p is responsible for TPase activity and the C-terminal part is essential for GTase activity. In addition, the human TPase domain cannot functionally substitute for the yeast enzyme in vivo.
A microrobotic system for colonoscopy (2002)

Colonoscopy is an important procedure for the diagnosis of various pathologies, in particular cancer of the colon and of the rectum, the second most malignant tumor in industrialized countries. At present however, colonoscopy is a procedure often painful for the patient and complex for the doctor. This is mainly due to the characteristics of current colonoscopes, which are quite rigid and require the doctor to perform difficult maneuvers for insertion. In this paper we present the concept and describe the design and fabrication of a new system for colonoscopy based on a microrobot capable of being propelled semi-autonomously along the colon. The microrobot system comprises a mothership incorporating devices for clamping the colon wall and tools for diagnosis and intervention. The actuation system is based on purposely developed shape memory alloy (SMA) pneumatic microvalves. A human/machine interface allows the doctor to teleoperate or supervise the functioning of the microrobot and to receive visual and other information during endoscopy. Particular attention has been paid to investigating a reliable and safe method of locomotion and to develop an efficient clamping system for the microrobot. The resulting configuration of the microrobot is very simple and potentially suitable for real clinical application. A prototype microrobot system has been tested in vitro with promising results.
Diabetic foot ulcers: A framework for prevention and care (1999)

Complications secondary to diabetes, such as diabetic foot ulcers, continue to be a major worldwide health problem. At the same time, health care systems are changing rapidly, causing concern about the quality of patient care. While the ultimate effect of current changes on health care professionals and patient outcomes remain uncertain, measures commonly used to reduce costs, e.g., disease and multi- disciplinary management strategies, have been shown to help prevent the occurrence of diabetic ulcers. In addition, utilizing a multi- disciplinary approach, the principles of off-loading and optimal wound care, the vast majority of diabetic foot ulcers can be expected to heal within 12 weeks of treatment. Education of primary care providers and patients is paramount.
Arteriogenesis Versus Angiogenesis: Two Mechanisms of Vessel Growth (1999)

After birth, new blood vessel formation proceeds via angiogenesis or arteriogenesis. Angiogenesis (capillary sprouting) results in higher capillary density. Arteriogenesis (rapid proliferation of collateral arteries) is potentially able to significantly alter the outcome of coronary and peripheral artery disease. The processes share some growth features but differ in many aspects.
The HrpZ Proteins ofPseudomonas syringaepvs.syringae, glycinea,andtomatoAre Encoded by an Operon ContainingYersinia yscHomologs and Elicit the Hypersensitive Response in Tomato but not Soybean (1995)

The Pseudomonas syringae pathovars are composed of host-specific plant pathogens that characteristically elicit the defense-associated hypersensitive response (HR) in nonhost plants. P. s. pv. syringae 61 secretes an HR elicitor, harpinPss (HrpZPss), in a hrp-dependent manner. An internal fragment of the P. s. pv. syringae 61 hrpZ gene was used to clone the hrpZ locus from P. s. pv. glycinea race 4 (bacterial blight of soybean) and P. s. pv. tomato DC3000 (bacterial speck of tomato). DNA sequence analysis revealed that hrpZ is the second ORF in a polycistronic operon. The amino acid sequence identities of HrpZPss/HrpZPsg and HrpZPss/HrpZPst were 79 and 63%, respectively. Although none of the HrpZ proteins showed significant overall sequence similarity with other known proteins, HrpZPst contained a 24-amino acid sequence that is homologous with a region of the PopA1 elicitor protein of the tomato pathogen, Pseudomonas solanacearum GMI1000. hrpA, the upstream ORF, was highly divergent: The amino acid sequence identities of HrpAPss/HrpAPsg and HrpAPss/HrpAPst were 91 and 28%, respectively, and no HrpA sequence showed similarity to known proteins. In contrast, the predicted products of the downstream ORFs in P. s. pv. syringae and P. s. pv. tomato, hrpB, hrpC, hrpD, and hrpE showed varying levels of similarity to those of yscI, yscJ, yscK, and yscL. These are colinearly arranged genes in the virC locus of Yersinia spp., which are involved in the secretion of the Yop virulence proteins via the type III pathway. The similarity of the Ysc proteins was generally stronger in comparisons with the P. s. pv. tomato Hrp proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
[Complex characterization of the influence of environmental factors and social conditions on population health]. (2006)

The study determined the overall contribution of atmospheric air pollution and socioeconomic and other factors on population health, as well as the role of medical providence in the lowering of population morbidity. The study shows that different individual factors of medical providence have different effects on medicodemographic situation. Also different is the significance of various characteristics of socioeconomic conditions. The results demonstrate that the contribution of air pollutants and their mixtures into male and female mortality in various age groups is different and depends on the cause of death and pathogenetic peculiarities of the action of the components.
Overcoming the Lack of Parallel Data in Sentence Compression (2013)

A major challenge in supervised sentence compression is making use of rich feature representations because of very scarce parallel data.We address this problem and present a method to automatically build a compression corpus with hundreds of thousands of instances on which deletion-based algorithms can be trained.In our corpus, the syntactic trees of the compressions are subtrees of their uncompressed counterparts, and hence supervised systems which require a structural alignment between the input and output can be successfully trained.We also extend an existing unsupervised compression method with a learning module.The new system uses structured prediction to learn from lexical, syntactic and other features.An evaluation with human raters shows that the presented data harvesting method indeed produces a parallel corpus of high quality.Also, the supervised system trained on this corpus gets high scores both from human raters and in an automatic evaluation setting, significantly outperforming a strong baseline.
To Eat or Not to Eat — How the Gut Talks to the Brain (2003)

New insights into the complex metabolic circuitry of energy homeostasis have refined our understanding of the pathophysiology of obesity. Some of these insights regarding energy homeostasis are based on the identification of new functions for peptides that were discovered decades ago (see Figure). It is now known that α-melanocyte–stimulating hormone, a peptide derived from proopiomelanocortin and long recognized for its role in skin pigmentation through activity at the melanocortin 1 receptor (MC1R), decreases food intake and increases energy expenditure through interaction in the hypothalamus with another melanocortin receptor, MC4R. In mice, targeted deletion of the Mc4r gene results in obesity, . . .
Discovery of a Novel A2BAdenosine Receptor Antagonist as a Clinical Candidate for Chronic Inflammatory Airway Diseases (2008)

Recently, we have reported a series of new 1,3-symmetrically (R 1 = R 3) substituted xanthines ( 3 and 4) which have high affinity and selectivity for the human adenosine A 2B receptors (hA(2B)-AdoR). Unfortunately, this class of compounds had poor pharmacokinetic properties. This prompted us to investigate the effect of differential alkyl substitution at the N-1 and N-3 positions ( N 1-R not equal to N 3-R) on A(2B)-AdoR affinity and selectivity; we had the dual objectives of enhancing affinity and selectivity for the A(2B)-AdoR, as well as improving oral bioavailability. This effort has led to the discovery of compound 62, that displayed high affinity and selectivity for the hA(2B)-AdoR (K(i) = 22 nM). In addition, compound 62 showed high functional potency in inhibiting the accumulation of cyclic adenosine monophosphate induced by 5'- N-ethylcarboxamidoadenosine in HEK-A(2B)-AdoR and NIH3T3 cells with K(B) values of 6 and 2 nM, respectively. In a single ascending-dose phase I clinical study, compound 62 had no serious adverse events and was well tolerated.
Comparison of two host cell range variants of feline immunodeficiency virus (1990)

Two molecular clones of feline immunodeficiency virus were compared. The first clone, 34TF10, was from a Petaluma, Calif., isolate; the second, PPR, was isolated from a cat in the San Diego, Calif., area. The cats from which the isolates were obtained suffered from chronic debilitating illnesses. The two molecular clones differed in their in vitro host cell range. The 34TF10 clone infected the Crandall feline kidney and G355-5 cell lines, but replicated less efficiently on feline peripheral blood leukocytes. In contrast, the PPR clone productively infected the primary feline peripheral blood leukocytes but not Crandall feline kidney or G355-5 cells. The 34TF10 and PPR clones had an overall sequence identity of 91%. The env gene was the least conserved (85% at the amino acid level). Additionally, the potential open reading frame for a Tat-like protein, ORF 2, contained a stop codon in the 34TF10 isolate which was not found in the PPR clone. This truncation did not prevent in vitro or in vivo replication of 34TF10. Two splice acceptor sites were identified in the 34TF10 clone. One was 5' to the beginning of the putative tat open reading frame, and the other was 5' to the putative vif product. Both of these acceptor sites were conserved in the PPR clone. The long terminal repeats of the viruses were 7% divergent between the two clones, with a lack of conservation in putative NF-kappa B, LBP-1, and CCAAT enhancer-promoter sites.
Some recent trends and progress in nucleoside synthesis. (1996)

Some recent progress concerning the optimal combinations of Lewis acids and solvents for the synthesis of pyrimidine as well as purine nucleosides is reviewed. Furthermore, the novel condensation of persilylated free sugars and heterocyclic bases in the presence of trimethylsilyl triflate to the corresponding persilylated nucleosides is discussed.
Opposing Effects on Modulation of Angiogenesis by Protein Kinase C and cAMP-Mediated Pathways (1994)

The role of cAMP-mediated pathway in modulating angiogenesis was investigated. We have shown previously that activators of protein kinase C (PKC) caused a marked increase in angiogenesis, while the specific inhibitor of PKC, Ro 318220 suppressed angiogenesis. Here we show that forskolin, which activates adenylate cyclase and elevates the intracellular levels of cAMP, and the Sp-diastereomer of adenosine cyclic-3',5'-monophosphothioate (Sp-cAMPS), caused a dose-dependent suppression of collagenous protein biosynthesis and angiogenesis in the chick chorioallantoic membrane system (CAM). The opposite modulation of angiogenesis by activators of PKC and elevated cAMP levels was further confirmed by the suppression of 4 beta-phorbol-12-myristate-13-acetate (4 beta-PMA)-stimulated angiogenesis by either forskolin or Sp-cAMPS. On the contrary, the Rp-diastereomer of adenosine cyclic-3',5'-monophosphothioate (Rp-cAMPS), which antagonises endogenous cAMP biochemical actions, had no effect on angiogenesis alone and did not suppress 4 beta-PMA stimulated angiogenesis. However, Rp-cAMPS antagonised the effect of forskolin and Sp-cAMPS on 4 beta-PMA induced angiogenesis. Similar results were obtained in the human umbilical vein endothelial cell tube formation assay. In this system, the PKC inhibitor, Ro 318220, caused a dose-dependent inhibition of 4 beta-PMA reversed this effect. Also, forskolin and Sp-cAMPS caused an inhibition in tube formation. These results indicate that increased levels of intracellular cAMP have a negative effect in normal angiogenesis and cause a large reduction of the promotion of angiogenesis resulting from PKC activation.
Targeting protease activated receptor-1 with P1pal-12 limits bleomycin-induced pulmonary fibrosis (2013)

Overall, targeting PAR-1 may be a promising treatment for pulmonary fibrosis.
A rotational comb-driven micromirror with a large deflection angle and low drive voltage (2003)

We have designed, fabricated, and tested a V-shaped torsion bar for use with a comb-driven micromirror. This torsion bar suppressed undesired sticking of the comb teeth, and enabled a large rotational angle and a low drive voltage. We observed 5-degree rotation of a comb-driven micromirror with a drive voltage of 90 V.
Upscaling: a review (2002)

Abstract Porous media have properties with heterogeneities on several length scales. It is possible to build digital models of such properties. However these can be so detailed that a computing machine of the same power as that used to build the property model is not able to solve the fluid flow equations using standard discretisation methods—storage is needed for workspace, and the discrete equations have to be solved in a reasonable time. This paper reviews averaging techniques, devised to simulate large scale features of solutions without necessarily solving all the fine scale equations. Copyright © 2002 John Wiley &amp; Sons, Ltd.