gebhart/patrepeval huggingface dataset:
Stimulation of synthesis and secretion of chorionic gonadotropin subunits by eutopic and ectopic hormone-producing human cell lines. (1980)

The effects of dibutyryl cyclic adenosine 3'3':-5'-monophosphate (AMP) and sodium butyrate on the synthesis and secretion of human chorionic gonadotropin (HCG) by trophoblastic and nontrophoblastic human cell lines were studied by radioimmunoassay and pulse-chase labeling techniques. Dibutyryl cyclic AMP stimulated synthesis and secretion of HCG-alpha and HCG-beta subunits by the trophoblastic cell lines JAR and BeWo, whereas butyrate had no effect or decreased secretion. On the other hand, a number of nontrophoblastic cell lines (including the breast carcinoma lines ZR-75-31, BT-20, and MCF-7; the bronchogenic carcinoma line ChaGo; and the cervical carcinoma line HeLa S3) were induced to synthesize and secrete increased amounts of HCG subunits by butyrate, but dibutyryl cyclic AMP had less or no stimulatory effect. The nontrophoblastic brain tumor line CBT was an exception to this general rule in that HCG-beta production was stimulated by dibutyryl cyclic AMP but not by butyrate. In all cases, the drug-induced increase in HCG subunit secretion was directly proportional to the elevation of HCG subunit synthesis. These data suggest that the differential effects of dibutyryl cyclic AMP and butyrate on trophoblastic and nontrophoblastic cells reflect differences in the transcription or translation of HCG subunit genes induced by these agents in the two cell types.
Sniffing the Unique “Odor Print” of Non‐Small‐Cell Lung Cancer with Gold Nanoparticles (2009)

A highly sensitive and fast-response array of sensors based on gold nanoparticles, in combination with pattern recognition methods, can distinguish between the odor prints of non-small-cell lung cancer and negative controls with 100% accuracy, with no need for preconcentration techniques. Additionally, preliminary results indicate that the same array of sensors might serve as a better tool for understanding the biochemical source of volatile organic compounds that might occur in cancer cells and appear in the exhaled breath, as compared to traditional spectrometry techniques. The reported results provide a launching pad to initiate a bedside tool that might be able to screen for early stages of lung cancer and allow higher cure rates. In addition, such a tool might be used for the immediate diagnosis of fresh (frozen) tissues of lung cancer in operating rooms, where a dichotomic diagnosis is crucial to guide surgeons.
Cryptosporidiosis in Immunocompetent Patients (1985)

The intestinal protozoan cryptosporidium is known to cause diarrhea in immunocompromised patients, but few cases have been reported in detail in immunocompetent persons. During a 12-month period, we identified cryptosporidium in the stools of 43 immunocompetent patients. The numbers of cases were increased in those under 4 years old and in those from 30 to 39 years old. Of 30 index cases, 23 (77 per cent) were diagnosed in the late summer or the fall. Fifteen of the 43 patients (35 per cent) had other gastrointestinal pathogens, of which only Giardia lamblia was statistically associated with cryptosporidium. In the 28 patients in whom other gastrointestinal pathogens were not identified, the clinical manifestations were predominantly watery, nonbloody diarrhea and, less commonly, abdominal discomfort, anorexia, fever, nausea, and weight loss. The infection was self-limited in all 43 patients. Clustering of cases occurred in a day-care center and in two families. These clinical observations confirm worldwide findings and suggest that cryptosporidium is a relatively common nonviral cause of self-limited diarrhea in immunocompetent persons in the northeastern United States.
Pattern Transformation of Heat-Shrinkable Polymer by Three-Dimensional (3D) Printing Technique (2015)

A significant challenge in conventional heat-shrinkable polymers is to produce controllable microstructures. Here we report that the polymer material fabricated by three-dimensional (3D) printing technique has a heat-shrinkable property, whose initial microstructure can undergo a spontaneous pattern transformation under heating. The underlying mechanism is revealed by evaluating internal strain of the printed polymer from its fabricating process. It is shown that a uniform internal strain is stored in the polymer during the printing process and can be released when heated above its glass transition temperature. Furthermore, the internal strain can be used to trigger the pattern transformation of the heat-shrinkable polymer in a controllable way. Our work provides insightful ideas to understand a novel mechanism on the heat-shrinkable effect of printed material, but also to present a simple approach to fabricate heat-shrinkable polymer with a controllable thermo-structural response.
Heterodimeric complex formation with CD8 and TCR by bispecific antibody sustains paracrine IL-2-dependent growth of CD3+ CD8+ T cells (1992)

During physiologic activation of mature CD8+ T cells, TCR and CD8 bind to the same Ag-complexed MHC class I molecule. Thereby, close proximity is induced between CD8 and the TCR/CD3 complex. During this engagement, CD8 may deliver TCR-independent signals via its associated protein tyrosine kinase, p56lck. We studied the potential biologic effects of close association between CD8 and TCR/CD3 complexes by using a bispecific antibody (bsAb) directed against both TCR and CD8 molecules. This hybrid hybridoma (quadroma)-produced bsAb binds as a monomeric molecule to CD3+ CD8+ but not CD3+ CD4+ T cells. The bsAb proved capable of inducing the cytotoxic effector function of cloned CD3+ CD8+ T cells but not of CD3+ CD4+ T cells. When the bsAb was presented to resting T cells by monocytes, proliferation of the CD3+ CD4+ but not the CD3+ CD8+ subset of T lymphocytes was induced. Parental anti-TCR antibody induced vigorous growth of cells of both subsets. Essentially identical results were obtained when bsAb was presented in an immobilized fashion. The unresponsiveness of the CD3+ CD8+ T cells with respect to mitogenesis could be restored by exogenous rIL-2. The data suggest that bsAb-induced activation differs from activation by monospecific anti-TCR antibody. The former appears to more closely mimic physiologic Ag-induced signaling, because it leads to a similar paracrine IL-2-dependent growth pattern. The bsAb may, therefore, be instrumental in studying T cell signaling pathways, in particular the role of CD8-associated p56lck therein.
High internal phase emulsions (HIPEs) containing divinylbenzene and 4-vinylbenzyl chloride and the morphology of the resulting PolyHIPE materials (2000)

The cell size of DVB–VBC PolyHIPEs decreases with increasing VBC content, which appears to be due to the adsorption of VBC at the emulsion interface leading to a lower interfacial tension and a smaller droplet size.
Tumor Growth Need Not Be Driven by Rare Cancer Stem Cells (2007)

The cancer stem cell hypothesis postulates that tumor growth is driven by a rare subpopulation of tumor cells. Much of the supporting evidence for this intriguing idea is derived from xenotransplantation experiments in which human leukemia cells are grown in immunocompromised mice. We show that, when lymphomas and leukemias of mouse origin are transplanted into histocompatible mice, a very high frequency (at least 1 in 10) of the tumor cells can seed tumor growth. We suggest that the low frequency of tumor-sustaining cells observed in xenotransplantation studies may reflect the limited ability of human tumor cells to adapt to growth in a foreign (mouse) milieu.
Influence of adipocyte isolation by collagenase on phosphodiesterase activity and lipolysis in man (1980)

The maximum phosphodiesterase activity (Vmax) with low and high Km was, respectively, 10- and 3-times greater in tissue fragments than in collagenase-isolated adipocytes obtained from subcutaneous fat layers in man. The exposure of such tissue fragments to collagenase of various origins in order to isolate the fat cells resulted in a 60-70% inhibition of phosphodiesterase (PDE) activity. Noradrenaline- and isopropyl noradrenaline-induced rates of lipolysis were more rapid in the isolated fat cells than in the tissue fragments. The sensitivity to catecholamines, however, was the same for the two tissue preparations. Nor did they differ in respect to the effect of theophylline, a PDE inhibitor, on the rate of lipolysis. The time curve for cyclic AMP accumulation was significantly higher in the isolated adipocytes than in tissue fragments in the presence of isopropyl noradrenaline. It is concluded that the greater lipolytic response of collagenase-isolated adipocytes than of tissue fragments to catecholamines may be attributed, at least in some measure, to the higher concentration of cyclic AMP resulting from a decrease in PDE activity.
The nucleotide sequence of the chick cytoplasmic β-actin gene (1983)

The nucleotide sequence of the chick beta-actin gene was determined. The gene contains 5 introns; 4 interrupt the translated region at codons 41/42, 120/122, 267, 327/328 and a large intron occurs in the 5' untranslated region. The gene has a 97 nucleotide 5'-untranslated region and a 594 nucleotide 3'-untranslated region. A slight heterogeneity in the position of the poly A addition site exists; polyadenylation can occur at either of two positions two nucleotides apart. The gene codes for an mRNA of 1814 or 1816 nucleotides, excluding the poly(A) tail. In contrast to the chick skeletal muscle actin gene the beta-actin gene lacks the Cys codon between the initiator ATG and the codon for the N-terminal amino acid of the mature protein. In the 5' flanking DNA, 15 nucleotides downstream from the CCAAT sequence, is a tract of 25 nucleotides that is highly homologous to the sequence found in the same region of the rat beta-actin gene.
Structural and Biochemical Characterization of Plasmodium falciparum 12 (Pf12) Reveals a Unique Interdomain Organization and the Potential for an Antiparallel Arrangement with Pf41 (2013)

Plasmodium falciparum is the most devastating agent of human malaria. A major contributor to its virulence is a complex lifecycle with multiple parasite forms, each presenting a different repertoire of surface antigens. Importantly, members of the 6-Cys s48/45 family of proteins are found on the surface of P. falciparum in every stage, and several of these antigens have been investigated as vaccine targets. Pf12 is the archetypal member of the 6-Cys protein family, containing just two s48/45 domains, whereas other members have up to 14 of these domains. Pf12 is strongly recognized by immune sera from naturally infected patients. Here we show that Pf12 is highly conserved and under purifying selection. Immunofluorescence data reveals a punctate staining pattern with an apical organization in late schizonts. Together, these data are consistent with an important functional role for Pf12 in parasite-host cell attachment or invasion. To infer the structural and functional diversity between Pf12 and the other 11 6-Cys domain proteins, we solved the 1.90 Å resolution crystal structure of the Pf12 ectodomain. Structural analysis reveals a unique organization between the membrane proximal and membrane distal domains and clear homology with the SRS-domain containing proteins of Toxoplasma gondii. Cross-linking and mass spectrometry confirm the previously identified Pf12-Pf41 heterodimeric complex, and analysis of individual cross-links supports an unexpected antiparallel organization. Collectively, the localization and structure of Pf12 and details of its interaction with Pf41 reveal important insight into the structural and functional properties of this archetypal member of the 6-Cys protein family.
Noncovalent Immobilization of Electrocatalysts on Carbon Electrodes for Fuel Production (2013)

We show that molecular catalysts for fuel-forming reactions can be immobilized on graphitic carbon electrode surfaces via noncovalent interactions. A pyrene-appended bipyridine ligand (P) serves as the linker between each complex and the surface. Immobilization of a rhodium proton-reduction catalyst, [Cp*Rh(P)Cl]Cl (1), and a rhenium CO2-reduction catalyst, Re(P)(CO)3Cl (2), afford electrocatalytically active assemblies. X-ray photoelectron spectroscopy and electrochemistry confirm catalyst immobilization. Reduction of 1 in the presence of p-toluenesulfonic acid results in catalytic H2 production, while reduction of 2 in the presence of CO2 results in catalytic CO production.
Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1 (2002)

Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance. In contrast, DGAT1 deficiency did not affect energy and glucose metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a compensatory upregulation of DGAT2 expression in the absence of leptin. Our results suggest that inhibition of DGAT1 may be useful in treating insulin resistance and leptin resistance in human obesity.
Regulation of the Tertiary Structure and Function of Coagulation Factor IX by Magnesium(II) Ions (1995)

The indispensable role of Ca2+ ions in the maintenance of the functional tertiary structures of vitamin K-dependent coagulation factors has been definitively established but the participation of Mg2+ ions, another alkaline-earth metal that is present abundantly in blood plasma, in such a process is not yet understood. We show here that the Ca(2+)-stabilized conformation of coagulation factor IX undergoes a further conformational change upon binding of Mg2+ ions using three independent structural probes. The probes we used were (i) IX/X-bp, a snake venom anticoagulant that recognizes the Gla domains in coagulation factors IX and X, (ii) conformation-specific polyclonal antibodies against bovine factor IX, and (iii) monoclonal antibodies against the Gla domain of human factor IX. The binding of all these probes had an absolute requirement for Ca2+ ions, and Mg2+ ions alone were ineffective. However, when added together with Ca2+ ions, Mg2+ ions at physiological concentrations greatly augmented the binding of these probes to factor IX; the required concentration of Ca2+ ions was much reduced, and the affinity of each probe for factor IX was increased even in the presence of an excess of Ca2+ ions. These results suggest the presence of a Mg(2+)-specific binding site that does not interact with Ca2+ ions in factor IX. Furthermore, Mg2+ ions potentiated the susceptibility of factor IX to activation by factor XIa, concomitant with their effect on the conformation. Similarly, the required Ca2+ concentration was reduced by Mg2+ ions, and the rate of conversion to factor IXa was increased by Mg2+ ions in the presence of an excess of Ca2+ ions. At a saturating concentration of Ca2+ ions (5 mM), addition of 1 mM Mg2+ reduced the apparent Km value for factor IX from 0.31 to 0.18 microM, and in the presence of a physiological concentration of Ca2+ ions (1 mM), the reduction in Km by Mg2+ ions was far more striking (from 0.91 to 0.24 microM). The apparent Vmax values were hardly affected by Mg2+ ions. Our present data reveal a hitherto novel physiological role of the Mg2+ ions in plasma. Not only Ca2+ ions but also Mg2+ ions are important regulators of the stabilization of the native conformation of factor IX as well as of its efficient activation.
INFLAMMATORY CYTOKINE RESPONSES IN JUVENILE CHRONIC ARTHRITIS (1995)

The inflammatory cytokines interleukin 1 beta (IL-1 beta) interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha) and the anti-inflammatory peptide--the interleukin 1 (IL-1) receptor antagonist--were measured in the plasma of children with juvenile chronic arthritis (JCA). In the two subgroups studied (polyarticular JCA and systemic JCA), there was good correlation between laboratory measures of disease activity C-reactive protein (CRP), erythrocyte sedimentation rate and clinical scores for disease activity. Despite higher levels of CRP in the systemic group IL-1 beta levels were lower and regression analysis recorded a difference in the relationship between CRP and IL-1 beta within the two clinical groups. In contrast, IL-6 levels were high in the systemic group and correlated with disease activity. No such correlation was observed in the polyarticular group. Five children with systemic JCA were studied during the febrile phase of their illness. IL-6 levels rose and fell with the fever. TNF alpha levels also rose and fell but out of phase with the fever. In contrast IL-1 beta levels were either undetectable throughout the febrile episode or only became detectable as the temperature reduced to normal. The IL-1 receptor antagonist was usually found in 1000-fold excess over IL-1 beta, levels rising and falling with the fever. These results demonstrate difference in the cytokine profiles and acute phase protein responses in polyarticular and systemic JCA. This would suggest different pathogenic mechanisms for these two groups of JCA with IL-6 being the more important cytokine in systemic JCA.
Antibodies to non-beta regions of the beta-amyloid precursor protein detect a subset of senile plaques. (1991)

A central unresolved issue in Alzheimer's disease is the origin of the extracellular amyloid beta protein (A beta P) found in senile plaques and its relationship to the dystrophic neurites that intimately surround it. Here the presence and distribution within senile plaques of various epitopes of the beta-amyloid precursor protein (APP) are compared with the distribution of A beta P itself and markers for plaque neurites. Several principal findings emerge: 1) antibodies to regions of APP outside of A beta P ('APP antibodies') recognize only a subgroup of senile plaques; 2) within these plaques, APP antibodies label discrete globular and granular structures morphologically resembling neurites; 3) virtually all of the plaques labeled by APP antibodies also contain neurites reactive with antibodies to tau; 4) double labeling with anti-tau and an APP antibody shows that the neuritelike profiles stained by the APP antibody are always closely associated with tau-positive neurites within the same plaque and that a minority of profiles appear to be labeled by both antibodies; and 5) antibodies to different regions throughout APP label the same profiles within plaques, suggesting the presence of the full-length precursor. The authors conclude that only a subgroup of senile plaques contain APP epitopes and that the immunostained structures are neurites. Because many A beta P-containing plaques in neocortex, cerebellum, and striatum were found to be devoid of any APP labeling, as were vascular A beta P deposits, it is unlikely that the extracellular A beta P is principally derived from the APP found within dystrophic neurites. The immunodetection of apparently full-length APP, an axonally transported protein, in selected plaque neurites provides yet another protein marker of neuritic dystrophy, possibly indicative of an aberrant regenerative response.
Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery (2008)

Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide. Novel treatment strategies derived from increased knowledge of molecular oncology are constantly being developed to cure this disease. Here, we used phage display to identify a novel peptide (SP94), which binds specifically to hepatocellular carcinoma cells. In vitro, the phage clone PC94 was shown to bind to hepatocellular carcinoma cell lines by ELISA and flow cytometry analysis. In vivo, PC94 homed specifically to tumor tissues but not to normal visceral organs in severe combined immunodeficient mice bearing human hepatocellular carcinoma xenografts. This homing ability could be competitively inhibited by synthetic peptide, SP94. Immunohistochemical staining confirmed that PC94 localized to tumor tissues and that it could not be detected in SP94-competed tumor tissues. In addition, PC94 recognized the tumor tissue but not nontumor tissue in surgical specimens from hepatocellular carcinoma patients, with a positive rate of 61.3% (19 of 31). With the conjugation of SP94 and liposomal doxorubicin, the targeted drug delivery system enhanced the therapeutic efficacy against hepatocellular carcinoma xenografts through enhanced tumor apoptosis and decreased tumor angiogenesis. Our results indicate that SP94 has the potential to improve the systemic treatment of patients with advanced hepatocellular carcinoma.
The Acute Respiratory Distress Syndrome, Mechanical Ventilation, and the Prone Position (2001)

The acute respiratory distress syndrome is a devastating, often fatal inflammatory condition that probably affects more than a million patients throughout the world each year.1 Since its description over 30 years ago,2 this syndrome has claimed the attention of clinicians and researchers because it is associated with an extremely high mortality rate and is difficult to treat, and because the pathophysiology of the disorder is unique.The common denominator in the acute respiratory distress syndrome is hypoxemia. Virtually all affected patients require mechanical ventilation to improve arterial oxygenation and minimize the energy costs of breathing. Ironically, the focus on normalizing . . .
Effects of chromosomal inversion on cell fitness in Escherichia coli K-12. (1988)

In an effort to learn what factors might mitigate the establishment of Escherichia coli variants bearing major chromosomal rearrangements, we have examined the effects on cell growth of two inversions between rRNA operons. One of these inversions, IN(rrnD-rrnE), had been propagated in a commonly used subline of E. coli K-12 for approximately 30 yr before its discovery, a fact that illustrates the absence of obvious detrimental effects associated with the inversion. We found that culturing under conditions requiring repeated transition from stationary phase to rapid growth led to the replacement of IN(rrnD-rrnE) cells by cells that had undergone either of two types of additional chromosomal inversion: one type fully restored the wild-type order, while the other partially restored it. The partial reinversion was also between rrn operons, but it left a small transposition. The tendency for overgrowth by these revertants persisted through several rounds of periodic selection. In contrast, the other inversion, IN(rrnG-rrnE), was associated with severe, detrimental effects. The effects of IN(rrnG-rrnE) were also alleviated by full or partial reinversion. The probable relationship between the severity of the effects caused by the inversions and the degree of displacement of the replication origin is discussed. Spontaneous inversion events between rrn operons separated by 18% of the chromosome were estimated to occur at a frequency of roughly 10(-5). If extended to natural situations, the growth disadvantage together with the relatively high frequency of reinversion suggest that clones of cells with an inversion between these rrn operons would be readily overgrown by revertants.
Bilateral Thoracoscopic Splanchnicectomy: Effects on Pancreatic Pain and Function (1999)

Bilateral thoracoscopic splanchnicectomy is beneficial in the treatment of pancreatic pain and is not associated with deterioration of pancreatic function.