gebhart/patrepeval huggingface dataset:
Synthesis of crystals with a programmable kinetic barrier to nucleation (2007)

A central goal of chemistry is to fabricate supramolecular structures of defined function and composition. In biology, control of supramolecular synthesis is often achieved through precise control over nucleation and growth processes: A seed molecule initiates growth of a structure, but this growth is kinetically inhibited in the seed's absence. Here we show how such control can be systematically designed into self-assembling structures made of DNA tiles. These structures, "zig-zag ribbons," are designed to have a fixed width but can grow arbitrarily long. Under slightly supersaturated conditions, theory predicts that elongation is always favorable but that nucleation rates decrease exponentially with increasing width. We confirm experimentally that although ribbons of different widths have similar thermodynamics, nucleation rates decrease for wider ribbons. It is therefore possible to program the nucleation rate by choosing a ribbon width. The presence of a seed molecule, a stabilized version of the presumed critical nucleus, removes the kinetic barrier to nucleation of a ribbon. Thus, we demonstrate the ability to grow supramolecular structures from rationally designed seeds, while suppressing spurious nucleation. Control over DNA tile nucleation allows for proper initiation of algorithmic crystal growth, which could lead to the high-yield synthesis of micrometer-scale structures with complex programmed features. More generally, this work shows how a self-assembly subroutine can be initiated.
Deep learning mutation prediction enables early stage lung cancer detection in liquid biopsy (2018)

Somatic cancer mutation detection at ultra-low variant allele frequencies (VAFs) is an unmet challenge that is intractable with current state-of-the-art mutation calling methods. Specifically, the limit of VAF detection is closely related to the depth of coverage, due to the requirement of multiple supporting reads in extant methods, precluding the detection of mutations at VAFs that are orders of magnitude lower than the depth of coverage. Nevertheless, the ability to detect cancer-associated mutations in ultra low VAFs is a fundamental requirement for low-tumor burden cancer diagnostics applications such as early detection, monitoring, and therapy nomination using liquid biopsy methods (cell-free DNA). Here we defined a spatial representation of sequencing information adapted for convolutional architecture that enables variant detection at VAFs, in a manner independent of the depth of sequencing. This method enables the detection of cancer mutations even in VAFs as low as 10x-4^, >2 orders of magnitude below the current state-of-the-art. We validated our method on both simulated plasma and on clinical cfDNA plasma samples from cancer patients and non-cancer controls. This method introduces a new domain within bioinformatics and personalized medicine – somatic whole genome mutation calling for liquid biopsy.
Liquid-jet target for laser-plasma soft x-ray generation (1996)

We describe a new liquid-target system for low-debris laser-plasma soft x-ray sources. The system is based on a microscopic liquid jet and is experimentally evaluated for 0.7–1 keV proximity lithography and water-window x-ray microscopy applications. Compared to an existing liquid-droplet target, this target system has the same low debris emission, high x-ray photon flux, and narrow spectral bandwidth. The advantages of the liquid-jet target include improved x-ray flux stability, increased range of suitable target liquids, and elimination of the need for temporal synchronization, thereby allowing less complex laser systems to be used.
Deuterium NMR and morphology study of polymer-dispersed liquid-crystal Bragg gratings (1996)

The orientational order in polymer-dispersed liquid crystals on holographically written volume Bragg gratings is studied using deuterium NMR. Unique spectral patterns indicate that a homeotropic liquid-crystal director configuration at the polymer interface is retained despite the small pore size ( < 100 nm). This structure coexists with liquid crystals in trapped defect structures of dimension comparable to the pore size.
Genetically engineered dendritic cell-based cancer vaccines (Review) (2001)

Dendritic cells (DCs) are the most potent professional antigen-presenting cells with exquisite capacity to interact with T cells and initiate their responses; the antigen-presenting capabilities of DCs make them attractive vehicles for the delivery of therapeutic cancer vaccines. The working hypothesis for utilization of DC-based cancer vaccines is that lack of efficient tumour antigen presentation on mature DCs, which is frequently observed in tumour-bearing individuals, can be bypassed by direct loading of DCs with oncoproteins in vitro, thus ensuring the transfer of immunostimulatory peptides on the respective antigen-presenting molecules. To enhance loading of DCs with oncoproteins in vitro and to increase the efficacy of the vaccines, a variety of genetic manipulations have been proposed and shown to be efficient in experimental tumour models. DCs were transfected either with polynucleotides, DNA or RNA, coding for tumour-associated antigens (TAAs), or with DNA encoding immunostimulatory cytokines and co-stimulatory molecules. The delivery of genes coding for antigenic epitopes or other molecules with a recombinant retrovirus, adenovirus, or poxvirus into dendritic cells has also been used for transduction and therapy. As an alternative method for TAA delivery into DCs, fusion of DCs with tumour cells has been utilized and the hybrid cell-based vaccines have been found to be highly therapeutically active, even in cancer patients. The purpose of this review is to summarize the approaches used for making and utilization of the genetically engineered DC-based cancer vaccines, to evaluate the therapeutic results obtained with the vaccines, and to discuss prospects and limitations of the vaccination.
Personalized Profile Based Search Interface With Ranked and Clustered Display (2001)

We have developed an experimental meta-search engine, which takes the snippets from traditional search engines and presents them to the user either in the form of clusters, indices or re-ranked list optionally based on the user's profile. The system also allows the user to give positive or negative feedback on the documents, clusters and indices. The architecture allows different algorithms for each of the features to be plugged-in easily, i.e. various clustering, indexing and relevance feedback algorithms, and profiling methods.
Comparison of β-Blockers, Amiodarone Plus β-Blockers, or Sotalol for Prevention of Shocks From Implantable Cardioverter Defibrillators<SUBTITLE>The OPTIC Study: A Randomized Trial</SUBTITLE> (2006)

Despite use of advanced ICD technology and treatment with a beta-blocker, shocks occur commonly in the first year after ICD implant. Amiodarone plus beta-blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00257959.
Biologically useful chelators that release Ca2+ upon illumination (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiologically useful chelators that release Ca2+ upon illuminationS. R. Adams, Joseph P. Y. Kao, G. Grynkiewicz, A. Minta, and R. Y. TsienCite this: J. Am. Chem. Soc. 1988, 110, 10, 3212–3220Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/ja00218a034https://doi.org/10.1021/ja00218a034research-articleACS PublicationsRequest reuse permissionsArticle Views1442Altmetric-Citations205LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
What can we learn about human immunodeficiency virus infection from a study of lymphocytic choriomeningitis virus? (1997)

The role of cytotoxic T lymphocytes (CTL) in human immunodeficiency virus (HIV) infection remains elusive. Since the discovery 10 years ago of high levels of specific CTL in this disease, some have argued that they play an important role in virus control, others that they drive disease progression through destruction of T helper cells, and others still that they play no obvious role at all. By contrast, the central role of CTL in murine lymphocytic choriomeningitis virus (LCMV) infection has been very clearly worked out through the use of in vivo depletion and adoptive transfer experiments, as well as knockout and transgenic mice. To interpret the possible roles for CTL in HIV, we have therefore made a comparison between what is known about CTL and their interaction with virus-infected cells in these two infections. This illustrates a potential critical role for these cells in both control of HIV replication and immune-mediated pathology, but one that is highly dependent on virus dose, distribution and dynamics.
Anti-Inflammatory Effects of the 70 kDa Heat Shock Protein in Experimental Stroke (2007)

The 70-kDa heat shock protein (Hsp70) is involved in protecting the brain from a variety of insults including stroke. Although the mechanism has been largely considered to be because of its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory responses. To explore how and whether Hsp70 regulate immune responses in brain ischemia, mice overexpressing Hsp70 (Hsp Tg) were subjected to 2 h middle cerebral artery occlusion, followed by 24 h reperfusion. Parallel experiments were performed using a brain inflammation model. Hsp Tg microglia cocultured with astrocytes were used to evaluate the direct effects of Hsp70 on cytotoxicity of mcrigolia. Compared with wild-type (Wt) littermates, Hsp Tg mice showed decreased infarct size and improved neurological deficits. The number of activated microglia/macrophages were also reduced in ischemic brains of Hsp Tg mice. Similar observations were made in a model of brain inflammation that does not result in brain cell death. Overexpression of Hsp70 in microglia completely prevented microglia-induced cytotoxicity to astrocytes. Activation of the inflammatory transcription factor, nuclear factor-κB (NF-κB) was inhibited significantly in Hsp Tg mice and microglia. This was associated with decreased phosphorylation of NF-κB inhibitor protein, IκBα, and decreased expression of several NFκB-regulated genes. Co-immunoprecipitation studies revealed an interaction of Hsp70 with NF-κB and IκBα, but not with IkB kinase, IKKγ, suggesting that Hsp70 binds to the NF-κB:IκB complex preventing IκB phosphorylation by IKK. The findings of the present work establish an anti-inflammatory role for Hsp70 in the context of brain ischemia as a novel mechanism of protection.
Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women (2006)

A 2-week course of 1% tenofovir vaginal gel used twice daily was well tolerated in sexually abstinent and sexually active HIV-negative and HIV-positive women. Systemic tenofovir absorption occurred. Expanded safety and effectiveness testing is warranted.
Carboxylic, Weak Acid Type, Cation Exchange Resin (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarboxylic, Weak Acid Type, Cation Exchange ResinRobert Kunin and Ruth E. BarryCite this: Ind. Eng. Chem. 1949, 41, 6, 1269–1272Publication Date (Print):June 1, 1949Publication History Published online1 May 2002Published inissue 1 June 1949https://pubs.acs.org/doi/10.1021/ie50474a028https://doi.org/10.1021/ie50474a028research-articleACS PublicationsRequest reuse permissionsArticle Views997Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Studies of biologic and serologic activities of rabbit-IgG antibody depleted of carbohydrate residues. (1973)

Rabbit IgG preparations containing antibody activity against individual strains of Staphylococcus aureus, Escherichia coli, group A β-hemolytic streptococci, and pneumococci were digested with Diplococcus pneumoniae endoglycosidase enzyme with removal of more than half of Ig-associated carbohydrate. In addition specifically purified rabbit anti-bovine serum albumin (BSA) IgG was similarly treated. After carbohydrate removal no appreciable change in opsonic, complement fixing, or agglutinating activity was noted in anti-staphylococcal, anti-E. coli, or anti-streptococcal IgG preparations, whereas complete loss of both complement fixing and opsonic activity occurred with rabbit IgG containing anti-pneumococcal antibody activity. No change in passive cutaneous anaphylactic reactions was noted after carbohydrate depletion of immunoabsorbent isolated rabbit anti-BSA IgG antibody. These findings indicate heterogeneous influences of carbohydrate residues on biologic activities of various antibody populations.
Systemic Counterregulatory Response of Placental Growth Factor Levels to Intravitreal Aflibercept Therapy (2015)

In this study, we report a significant systemic upregulation of the proangiogenic cytokine PlGF after intravitreal administration of aflibercept. This might represent a counter-regulatory response to antiangiogenic therapy.
Why a New Cancer Drug Works Well, In Some Patients (2004)

The deadliest cancer in many developed countries is lung cancer. In the United States, it kills roughly 160,000 men and women every year, largely because it has spread by the time it's diagnosed. Recently, however, a new drug called gefitinib (Iressa) has given patients a glimmer of hope, while presenting a puzzle: Iressa causes significant tumor shrinkage in only about 10% of the patients who take it, but when it does work, clinicians say, it works amazingly well. “We see a complete Lazarus type of response that we've never seen before,” says lung cancer specialist David Carbone of Vanderbilt University School of Medicine. New results now provide an explanation for why Iressa is so much more effective in some patients than others—information that should lead to better treatments for those patients and perhaps for other cancers as well.
Structural Transformation of Au−Pd Bimetallic Nanoclusters on Thermal Heating and Cooling:  A Dynamic Analysis (2006)

Classical molecular dynamics simulation is used for structural thermodynamic and dynamic analysis of Au-Pd bimetallic clusters. It is observed that the Pd-core/Au-shell structure is the most stable, and can be formed through annealing of other structures such as Au-core/Pd-shell, eutecticlike, or solid solution. Depending on the starting temperature and initial composition, three-layer icosahedral nanorod, face-centered cubic (fcc) nanorod, and fcc cluster can be obtained on slow cooling. The three-layer icosahedral nanorod structure is not as stable as the Pd-core/Au-shell decahedron; however it is more stable than the solid-solution decahedron structure up to 400 K. Our findings provide valuable insight into catalysis using Au-Pd and other similar bimetallic clusters.
Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis (2012)

miR 19b is a novel regulator of TGF-β signaling in HSCs, suggesting a potential therapeutic approach for hepatic fibrosis.
Monitoring chronic myeloid leukaemia therapy by real‐time quantitative PCR in blood is a reliable alternative to bone marrow cytogenetics (1999)

We have developed a rapid real-time quantitative PCR method for measuring BCR-ABL mRNA levels in peripheral blood in chronic myeloid leukaemia (CML). The technique was used to monitor minimal residual disease for the early detection of relapse and as an assessment of treatment response. Normal BCR mRNA was quantitated to control for RNA degradation and the results reported as a percentage of BCR-ABL/BCR. Every patient measured at diagnosis (n = 21) had increased expression of BCR-ABL of up to 5-fold above the normal BCR levels. With effective treatment the BCR-ABL levels decreased. The molecular data was correlated with Philadelphia chromosome levels in bone marrow and a good correlation was found when treatment induced a cytogenetic response (Spearman correlation = 0.94, P < 0.0001, n = 67 samples). In patients receiving interferon-alpha therapy we found a significant difference in the BCR-ABL levels between cytogenetic response groups. The method was sensitive, reproducible, and readily detected a change in BCR-ABL transcript levels in serial blood samples. Sample throughput was high because post PCR processing was unnecessary. We conclude that real-time quantitative PCR monitoring of peripheral blood can be used to reliably monitor disease response in CML.
Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK) (2001)

We have previously shown that the Drosophila Ste20 kinase encoded by misshapen (msn) is an essential gene in Drosophila development. msn function is required to activate the Drosophila c-Jun N-terminal kinase (JNK), basket (Bsk), to promote dorsal closure of the Drosophila embryo. Later in development, msn expression is required in photoreceptors in order for their axons to project normally. A mammalian homolog of msn, the NCK-interacting kinase (NIK) (recently renamed to mitogen-activated protein kinase kinase kinase kinase 4; Map4k4), has been shown to activate JNK and to bind the SH3 domains of the SH2/SH3 adapter NCK. To determine whether NIK also plays an essential role in mammalian development, we created mice deficient in NIK by homologous recombination at the Nik gene. Nik(-/-) mice die postgastrulation between embryonic day (E) 9.5 and E10.5. The most striking phenotype in Nik(-/-) embryos is the failure of mesodermal and endodermal cells that arise from the anterior end of the primitive streak (PS) to migrate to their correct location. As a result Nik(-/- )embryos fail to develop somites or a hindgut and are truncated posteriorly. Interestingly, chimeric analysis demonstrated that NIK has a cell nonautonomous function in stimulating migration of presomitic mesodermal cells away from the PS and a second cell autonomous function in stimulating the differentiation of presomitic mesoderm into dermomyotome. These findings indicate that despite the large number of Ste20 kinases in mammalian cells, members of this family play essential nonredundant function in regulating specific signaling pathways. In addition, these studies provide evidence that the signaling pathways regulated by these kinases are diverse and not limited to the activation of JNK because mesodermal and somite development are not perturbed in JNK1-, and JNK2-deficient mice.
Uniform Access to Distributed Name Interpretation in the V-System. (1984)

Tuberous sclerosis (TS) is a dominantly inherited disorder characterized by seizures, developmental delay, and specific skin lesions. Hypopigmented maculae that occur in 80% of patients with TS have become important for the clinical diagnosis of TS in young children. These lesions are claimed to be present from birth, in contrast with other dermatologic manifestations of TS that usually appear much later. We studied seven children in whom hypopigmented maculae appeared months to years after repeated negative skin examinations. Our findings emphasized that the absence of hypopigmented maculae in young children does not preclude their later appearance nor rule out the diagnosis of TS. The need for repeated skin examinations in infants and children with suspected TS or with seizures and/or mental retardation of unknown cause is apparent.
Novel Octahydropyrrolo[3,4-c]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate (2015)

The preclinical characterization of novel octahydropyrrolo[3,4-c]pyrroles that are potent and selective orexin-2 antagonists is described. Optimization of physicochemical and DMPK properties led to the discovery of compounds with tissue distribution and duration of action suitable for evaluation in the treatment of primary insomnia. These selective orexin-2 antagonists are proven to promote sleep in rats, and this work ultimately led to the identification of a compound that progressed into human clinical trials for the treatment of primary insomnia. The synthesis, SAR, and optimization of the pharmacokinetic properties of this series of compounds as well as the identification of the clinical candidate, JNJ-42847922 (34), are described herein.
Genioglossus activity available via non-arousal mechanisms vs. that required for opening the airway in obstructive apnea patients (2011)

It is generally believed that reflex recruitment of pharyngeal dilator muscles is insufficient to open the airway of obstructive apnea (OSA) patients once it is closed and, therefore, that arousal is required. Yet arousal promotes recurrence of obstruction. There is no information about how much dilator [genioglossus (GG)] activation is required to open the airway (GG Opening Threshold) or about the capacity of reflex mechanisms to increase dilator activity before/without arousal (Non-Arousal Activation). The relationship between these two variables is important for ventilatory stability. We measured both variables in 32 OSA patients (apnea-hypopnea index 74 ± 42 events/h). GG activity was monitored while patients were on optimal continuous positive airway pressure (CPAP). Zopiclone was administered to delay arousal. Maximum GG activity (GG(MAX)) and airway closing pressure (P(CRIT)) were measured. During stable sleep CPAP was decreased to 1 cmH(2)O to induce obstructive events and the dial-downs were maintained until the airway opened with or without arousal. GG activity at the instant of opening (GG Opening Threshold) was measured. GG Opening Threshold averaged only 10.4 ± 9.5% GG(Max) and did not correlate with P(CRIT) (r = 0.04). Twenty-six patients had >3 openings without arousal, indicating that Non-Arousal Activation can exceed GG Opening Threshold in the majority of patients. GG activity reached before arousal in Arousal-Associated Openings was only 5.4 ± 4.6% GG(MAX) below GG Opening Threshold. We conclude that in most patients GG activity required to open the airway is modest and can be reached by non-arousal mechanisms. Arousals occur in most cases just before non-arousal mechanisms manage to increase activity above GG Opening Threshold. Measures to reduce GG Opening Threshold even slightly may help stabilize breathing in many patients.