gebhart/patrepeval huggingface dataset:
Infiltration of tumors by systemically transferred tumor-reactive T lymphocytes is required for antitumor efficacy. (1999)

The systemic transfer of ex vivo-activated tumor-sensitized T lymphocytes can mediate immunologically specific regression of established tumors. However, it has not been conclusively established whether the infiltration of systemically transferred T cells into metastases is required for their effector function. In this study, T cells from lymph nodes draining the murine fibrosarcoma MCA 205 cells were activated ex vivo with anti-CD3 monoclonal antibody and interleukin-2. During the final 24 h of culture, the T cells were treated with pertussis toxin (PTX) to inhibit signaling through G protein-coupled chemokine receptors required for diapedesis. Systemically transferred PTX-treated cells did not have any therapeutic efficacy against 3-day established pulmonary metastases. This lack of efficacy correlated with their failure to infiltrate the tumor parenchyma. However, PTX-treated cells responded to tumor antigen stimulation with IFN-gamma secretion in vitro. More importantly, PTX-treated effector T cells prevented tumor growth when they were admixed with tumor cells and inoculated s.c. These results demonstrate that systemically transferred tumor-reactive T lymphocytes need to infiltrate the tumor parenchyma through the endothelium to initiate tumor regression, but PTX-sensitive proteins are not required for either antigen recognition or effector functions.
Emerging Clinical Applications of Microchip-Based Acoustophoresis (2011)

Acoustophoresis is currently in a state of transition from the academic laboratories, moving into the biomedical laboratories and industries. Clear areas of interest are seen in clinical diagnostics and therapeutics, where new approaches to cell handling and purification are emphasized as highly potent areas. This article outlines some of the basic unit operations of acoustophoresis, where applications as cell washing, binary separation, free-flow acoustophoresis, and affinity acoustophoresis are highlighted. The most recent steps to move acoustophoresis into clinical and preclinical applications are also presented.
HYPERTENSION CORRECTED AND ALDOSTERONE RESPONSIVENESS TO RENIN‐ANGIOTENSIN RESTORED BY LONG‐TERM DEXAMETHASONE IN GLUCOCORTICOID‐SUPPRESSIBLE HYPERALDOSTERONISM (1985)

Two males with glucocorticoid-suppressible hyperaldosteronism had hyperaldosteronism, hypertension and hypokalaemia corrected by continuous administration of physiological doses of dexamethasone for more than a year. During long-term dexamethasone treatment: (a) Plasma renin activity increased from subnormal to high normal levels, with normal posture-mediated increases; (b) Plasma aldosterone became responsive to angiotensin infusion, a new observation; (c) A fall in plasma aldosterone between 0800 h (recumbent) and 1000 h (upright) was replaced by a rise; (d) Plasma aldosterone became suppressible with salt loading. These findings are consistent with a shift to more normal control of aldosterone by renin-angiotensin, once abnormal responsiveness to ACTH has been nullified.
Continuous-flow matrix-assisted laser desorption ionization mass spectrometry (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTContinuous-flow matrix-assisted laser desorption ionization mass spectrometryLiang. Li, Alan P. L. Wang, and Larry D. CoulsonCite this: Anal. Chem. 1993, 65, 4, 493–495Publication Date (Print):February 15, 1993Publication History Published online1 May 2002Published inissue 15 February 1993https://pubs.acs.org/doi/10.1021/ac00052a029https://doi.org/10.1021/ac00052a029research-articleACS PublicationsRequest reuse permissionsArticle Views152Altmetric-Citations71LEARN 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
Synthesis of Comb Tri‐ and Tetrablock Copolymers Catalyzed by the Grubbs First Generation Catalyst (2009)

High molecular weight tri- and tetrablock copolymers were synthesized from the commercially available Grubbs first generation catalyst for the first time. These polymers had degrees of polymerization from 430 to 1 100, molecular weights up to 419 000 g · mol(-1) , and narrow polydispersities. Oxanorbornene monomers were chosen due to their fast rates of polymerization and slow rates of cross metathesis. Polystyrene arms were grown from selected blocks by atom transfer radical polymerization to yield architecturally complex comb tri- and tetrablock copolymers. These polymers self-assembled in the solid state into ordered morphologies that were characterized by scanning electron microscopy.
A Facile Preparation of 7-(Substituted amino)-6H-pyrrolo[3,4-d]pyrimidine Derivatives (1989)

Abstract 6-Phenyl-7-(substituted amino)-6H-pyrrolo[3,4-d]pyrimidine-2,4(1H,3H)-diones 3 were obtained by the reaction of 5-formyl-1,3-dimethyl-6-[(substituted amino)methyl]-2,4(1H,3H)-pyrimidinediones (1) with aniline (2a).
In vitro and in vivo activity of topotecan against human B-lineage acute lymphoblastic leukemia cells (1995)

Topotecan [(S)-9-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride; SK&F 104864-A, NSC 609699], a water soluble semisynthetic analogue of the alkaloid camptothecin, is a potent topoisomerase I inhibitor. Here we show that topotecan stabilizes topoisomerase I/DNA cleavable complexes in radiation-resistant human B-lineage acute lymphoblastic leukemia (ALL) cells, causes rapid apoptotic cell death despite high-level expression of bcl-2 protein, and inhibits ALL cell in vitro clonogenic growth in a dose-dependent fashion. Furthermore, topotecan elicited potent antileukemic activity in three different severe combined immunodeficiency (SCID) mouse models of human poor prognosis ALL and markedly improved event-free survival of SCID mice challenged with otherwise fatal doses of human leukemia cells at systemic drug exposure levels that can be easily achieved in children with leukemia.
Molecular markers for detection, surveillance and prognostication of bladder cancer (2008)

Many markers for the detection of bladder cancers have been tested and almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. Currently molecular and genetic changes play an important role in the discovery of new molecular markers for detection, prognostication and surveillance. The purpose of this review is to highlight the most important urinary molecular biomarker developments that have been studied and reported recently. In the current review we have summarized the most recent and relevant published reports on molecular urinary markers. The results of this review show that the first generation of urinary markers did not add much to urinary cytology. The current generation of markers is better, but additional clinical trials are needed. Our knowledge of molecular pathways in bladder cancer is growing and new methods of marker development emerge, but the perfect marker is still to be found. Currently, there are not clinically usable molecular markers that can guide us in diagnosis or surveillance, nor guide us in lowering the frequency of urethrocystoscopy in bladder cancer.
A fully integrated 1.9-GHz CMOS low-noise amplifier (1998)

A fully integrated 1.9 GHz CMOS low-noise amplifer (LNA) has been implemented in a 0.8 μm CMOS technology. For low-noise performance, the amplifier employs high-quality spiral inductors with a duality factor of 8.5-12.5, and device layout and bias condition of the active devices were optimized for low-noise conditions. This amplifier showed a noise figure of 2.8 dB with a forward gain of 15 dB at current consumption of 15 mA. To the authors' knowledge, this represents the lowest noise figure reported to date for a fully integrated CMOS LNA operating at 1.9 GHz.
Quality of life in anorexia nervosa, bulimia nervosa and eating disorder not-otherwise-specified (2013)

Patients with EDs have poor QoL and impairment increases with illness severity. Patients with binge/purge diagnoses are particularly impaired. It remains unclear which clinical features best predict the degree of impairment experienced by patients with EDs.
The ins and outs of fibronectin matrix assembly (2003)

Cell phenotype is specified by environmental cues embedded in the architecture and composition of the extracellular matrix (ECM). Much has been learned about matrix organization and assembly through analyses of the ECM protein fibronectin (FN). FN matrix assembly is a cell-mediated process in which soluble dimeric FN is converted into a fibrillar network. Binding of cell surface integrin receptors to FN converts it to an active form, which promotes fibril formation through interactions with other cell-associated FN dimers. As FN fibrils form on the outside of the cell, cytoplasmic domains of integrin receptors organize cytoplasmic proteins into functional complexes inside. Intracellular connections to the actin cytoskeletal network and stimulation of certain key intracellular signaling pathways are essential for FN-integrin interactions and propagation of FN fibril formation. Thus, assembly of native functional ECM depends on exquisite coordination between extracellular events and intracellular pathways.
Hypnotic analgesia: 1. somatosensory event-related potential changes to noxious stimuli and 2. transfer learning to reduce chronic low back pain (1998)

Fifteen adults with chronic low back pain (M = 4 years), age 18 to 43 years (M = 29 years), participated. All but one were moderately to highly hypnotizable (M = 7.87; modified 11-point Stanford Hypnotic Susceptibility Scale, Form C [Weitzenhoffer & Hilgard, 1962]), and significantly reduced pain perception following hypnotic analgesia instructions during cold-pressor pain training. In Part 1, somatosensory event-related potential correlates of noxious electrical stimulation were evaluated during attend and hypnotic analgesia (HA) conditions at anterior frontal (Fp1, Fp2), midfrontal (F3, F4), central (C3, C4), and parietal (P3, P4) regions. During HA, hypothesized inhibitory processing was evidenced by enhanced N140 in the anterior frontal region and by a prestimulus positive-ongoing contingent cortical potential at Fp1 only. During HA, decreased spatiotemporal perception was evidenced by reduced amplitudes of P200 (bilateral midfrontal and central, and left parietal) and P300 (right midfrontal and central). HA led to highly significant mean reductions in perceived sensory pain and distress. HA is an active process that requires inhibitory effort, dissociated from conscious awareness, where the anterior frontal cortex participates in a topographically specific inhibitory feedback circuit that cooperates in the allocation of thalamocortical activities. In Part 2, the authors document the development of self-efficacy through the successful transfer by participants of newly learned skills of experimental pain reduction to reduction of their own chronic pain. Over three experimental sessions, participants reported chronic pain reduction, increased psychological well-being, and increased sleep quality. The development of "neurosignatures of pain" can influence subsequent pain experiences (Coderre, Katz, Vaccarino, & Melzack, 1993; Melzack, 1993) and may be expanded in size and easily reactivated (Flor & Birbaumer, 1994; Melzack, 1991, 1993). Therefore, hypnosis and other psychological interventions need to be introduced early as adjuncts in medical treatments for onset pain before the development of chronic pain.
Isoform-specific Targeting and Interaction Domains in Human Nicotinamide Mononucleotide Adenylyltransferases (2010)

Several important signaling pathways require NAD as substrate, thereby leading to significant consumption of the molecule. Because NAD is also an essential redox carrier, its continuous resynthesis is vital. In higher eukaryotes, maintenance of compartmentalized NAD pools is critical, but so far rather little is known about the regulation and subcellular distribution of NAD biosynthetic enzymes. The key step in NAD biosynthesis is the formation of the dinucleotide by nicotinamide/nicotinic acid mononucleotide adenylyltransferases (NMNATs). The three human isoforms were localized to the nucleus, the Golgi complex, and mitochondria. Here, we show that their genes contain unique exons that encode isoform-specific domains to mediate subcellular targeting and post-translational modifications. These domains are dispensable for catalytic activity, consistent with their absence from NMNATs of lower organisms. We further demonstrate that the Golgi-associated NMNAT is palmitoylated at two adjacent cysteine residues of its isoform-specific domain and thereby anchored at the cytoplasmic surface, a potential mechanism to regulate the cytosolic NAD pool. Insertion of unique domains thus provides a yet unrecognized enzyme targeting mode, which has also been adapted to modulate subcellular NAD supply.
GRP receptors are present in non small cell lung cancer cells (1996)

Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small cell lung cancer (NSCLC) cells were investigated: (125I-Tyr4) bombesin (BN) or 125I-GRP bound with high affinity to NCI-H720 (lung carcinoid) and NCI-H1299 (large cell carcinoma) cells. Binding was specific, time dependent, and saturable. Specific (125I-Tyr4)BN binding to NCI-H1299 cells was inhibited with high affinity by GRP, BN, GRP14-27, (D-Phe6)BN6-13methyl ester, moderate affinity by NMB, and low affinity by GRP1-16. BN (10 nM) transiently elevated cytosolic calcium in a dose dependent manner. BN caused translocation of protein kinase C from the cytosol to the membrane and the translocation caused by BN was reversed by (D-Phe6)BN6-13methylester. BN stimulated arachidonic acid release and the increase caused by BN was reversed by (D-Phe6)BN6-13methylester. Using a clonogenic assay, BN stimulated the growth of NCI-H720 cells, and the number of colonies was reduced using (D-Phe6)BN6-13methylester. These data suggest that GRP receptors that are present in lung carcinoid and NSCLC cells may regulate proliferation.
ChemInform Abstract: Aminoalkylidene and Aminoalkyl Derivatives of 6,11‐Dihydrodibenzo(b,e)thiepin‐2‐ and ‐9‐carbonitrile and 4,10‐Dihydrothieno(2,3‐c)‐1‐benzothiepin‐6‐carbonitrile; Antidepressants with a New Activity Profile. (1988)

Abstract The title compounds (IVb), (VII)‐(XI), which are the cyano analogues of antidepressants of the prothiadene series, show properties of potential antidepressants and more or less inhibitors of the 5‐hydroxytryptamine uptake in the rat brain; at the same time they are rather strong central cholinolytics.
Activation of Phosphatidylinositol 3-Kinase Is Sufficient for Cell Cycle Entry and Promotes Cellular Changes Characteristic of Oncogenic Transformation (1998)

Using a new inducible form of phosphatidylinositol 3-kinase (PI 3-kinase) we have found that PI 3-kinase activation has the following effects on cell growth and proliferation. (i) Activation of PI 3-kinase was sufficient to promote entry into S phase of the cell cycle within several hours. This was shown by activation of cyclin-dependent kinase 4 (Cdk4) and Cdk2 and by the induction of DNA synthesis. (ii) PI 3-kinase activation alone was not, however, sufficient to provide for progression through the entire cell cycle. Instead, prolonged activation of PI 3-kinase in the absence of serum stimulation resulted in apoptosis. It is possible that the cells undergo apoptosis because the PI 3-kinase-induced entry into the cell cycle is abnormal. For example, we found that the cyclin E-Cdk2 complex, which normally disappears after entry into S phase of the cell cycle, fails to be downregulated following induction by PI 3-kinase. (iii) Finally, we found that prolonged activation of PI 3-kinase in the presence of serum resulted in cellular changes that resemble those associated with oncogenic transformation. The cells reached high densities, were irregular and refractile in appearance, and formed colonies in soft agar. In contrast, neither PI 3-kinase nor serum stimulation alone could induce these changes. Our results suggest that activation of PI 3-kinase promotes anchorage-independent cell growth and entry into the cell cycle but does not abrogate the growth factor requirement for cell proliferation.
In vitro expression in eukaryotic cells of a prion protein gene cloned from scrapie-infected mouse brain. (1988)

It has been proposed that the causative agent of scrapie represents a class of infectious particle that is devoid of nucleic acid and that an altered form of the endogenous prion protein (PrP) is the agent. However, it has been difficult to exclude the possibility that PrP purified from scrapie tissues might be contaminated with a more conventional viral agent. To obtain PrP uncontaminated by scrapie-infected tissues, PrP cDNA cloned from a scrapie-infected mouse brain was expressed in mouse C127 cells in vitro. mRNA and protein encoded by the cloned PrP gene were identified. The expressed PrP polypeptides appeared to be glycosylated and were released from the cell surface into the medium. Homogenates of the cells expressing the cloned PrP gene were inoculated into susceptible mice but failed to induce clinical signs of scrapie. Thus, either PrP is not the transmissible agent of scrapie or the expressed PrP requires additional modification to be infectious.
Sperm Sociality: Cooperation, Altruism, and Spite (2008)

The idea of subfertile or altogether infertile sperm seems an evolutionary paradox, so why have they evolved in a diverse set of species, from molluscs to mice? Understanding sperm sociality may provide the answer.
GRB2 and Phospholipase C-7γ1 Associate with a 36- to 38-Kilodalton Phosphotyrosine Protein after T-Cell Receptor Stimulation (1994)

GRB2, a 25-kDa protein comprising a single SH2 domain flanked by two SH3 domains, has been implicated in linking receptor protein tyrosine kinases (PTKs) to the Ras pathway by interacting with the guanine nucleotide exchange protein SOS. Previous studies have demonstrated that GRB2 directly interacts with Shc, a proto-oncogene product that is tyrosine phosphorylated upon receptor and nonreceptor PTK activation. In this report, we detected low levels of tyrosine phosphorylation of Shc and induced association with GRB2 upon T-cell receptor (TCR) stimulation. Instead, a prominent 36- to 38-kDa tyrosine phosphoprotein (pp36-38) associated with the SH2 domain of GRB2 and formed a stable complex with GRB2/SOS upon TCR stimulation. Cellular fractionation studies showed that whereas both GRB2 and SOS partitioned to the soluble and particulate fractions, pp36-38 was present exclusively in the particulate fraction. This phosphoprotein had the same apparent mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as the phosphoprotein that associates with phospholipase C-gamma 1 (PLC-gamma 1). Furthermore, following partial immunodepletion of GRB2 and of the associated pp36-38, there was a significant reduction in the amount of the 36-kDa phosphoprotein associated with PLC-gamma 1, suggesting that a trimeric PLC-gamma 1/pp36-38/GRB2 complex could form. In support of this notion, we have also been able to detect low levels of PLC-gamma 1 in GRB2 immunoprecipitates. We suggest that pp36-38 may be a bridging protein, coupling different signalling molecules to cytoplasmic PTKs regulated by the TCR.
Treatment of 283 Consecutive Patients With Metastatic Melanoma or Renal Cell Cancer Using High-Dose Bolus Interleukin 2 (1994)

Biologic therapy with IL-2 can cause significant antitumor effects in patients with advanced metastatic melanoma or renal cell cancer. Because IL-2 does not have a direct effect on cancer cells but rather mediates its antitumor activity by altering host immune reactions, these data represent the best available evidence that immunologic therapy for cancer can be effective in selected patients.
An Improved Method for the Isolation of Free‐Circulating Plasma DNA and Cell‐Free DNA from Other Body Fluids (2008)

Cell-free DNA is of increasing interest in different fields, such as cancer research, prenatal diagnosis, and the diagnosis of nonmalignant diseases. The quantity of free-circulating DNA in plasma, serum, and other body fluids is usually low and its isolation is still a challenge. Here we evaluate the application of the new commercially available NucleoSpin Plasma XS Kit for the isolation of cell-free DNA from plasma, serum, and cell-free bronchial lavage samples. The NucleoSpin columns proved superior to the QIAamp system in terms of DNA yield, purity, and retrieval of small DNA fragments. The procedure is fast and easy to standardize and might be valuable for laboratories working in the field of CNAPS.
A balance of FGF, BMP and WNT signalling positions the future placode territory in the head (2005)

The sensory nervous system in the vertebrate head arises from two different cell populations: neural crest and placodal cells. By contrast, in the trunk it originates from neural crest only. How do placode precursors become restricted exclusively to the head and how do multipotent ectodermal cells make the decision to become placodes or neural crest? At neural plate stages, future placode cells are confined to a narrow band in the head ectoderm, the pre-placodal region (PPR). Here, we identify the head mesoderm as the source of PPR inducing signals, reinforced by factors from the neural plate. We show that several independent signals are needed: attenuation of BMP and WNT is required for PPR formation. Together with activation of the FGF pathway, BMP and WNT antagonists can induce the PPR in naïve ectoderm. We also show that WNT signalling plays a crucial role in restricting placode formation to the head. Finally, we demonstrate that the decision of multipotent cells to become placode or neural crest precursors is mediated by WNT proteins: activation of the WNT pathway promotes the generation of neural crest at the expense of placodes. This mechanism explains how the placode territory becomes confined to the head, and how neural crest and placode fates diversify.
Barriers to Employment (2004)

This article reports on employment barriers experienced by random samples of 200 people who have left welfare and returned between June 1999 and May 2002, and 300 who left welfare between January 1999 and December 2001 and were not on state Department of Labor employment rolls. Demographic characteristics of returners and their reported barriers to employment (transportation 32 percent, not enough pay 29 percent, no jobs in the community 26 percent, negative attitudes of co-workers 32 percent, stressful working environments 29 percent) were consistent with Wilson's (1991) article and Vartanian's (1999a, 1999b) work on the effects of the neighborhood environment and lack of access. Leavers, on the other hand, reported higher degrees of physical disability (53 percent), illness or injury (44 percent), and mental illness (26 percent) as barriers to employment.
Bisphenol-A, an environmental estrogen, activates the human orphan nuclear receptor, steroid and xenobiotic receptor-mediated transcription (2001)

Our observations have indicated that BPA may be a human-specific inducer of the CYP3A4 gene, and may influence the metabolism of endogenous steroids, drugs, and other xenobiotics.