gebhart/patrepeval huggingface dataset:
Multi-day rhythms modulate seizure risk in epilepsy (2018)

Epilepsy is defined by the seemingly random occurrence of spontaneous seizures. The ability to anticipate seizures would enable preventative treatment strategies. A central but unresolved question concerns the relationship of seizure timing to fluctuating rates of interictal epileptiform discharges (here termed interictal epileptiform activity, IEA), a marker of brain irritability observed between seizures by electroencephalography (EEG). Here, in 37 subjects with an implanted brain stimulation device that detects IEA and seizures over years, we find that IEA oscillates with circadian and subject-specific multidien (multi-day) periods. Multidien periodicities, most commonly 20-30 days in duration, are robust and relatively stable for up to 10 years in men and women. We show that seizures occur preferentially during the rising phase of multidien IEA rhythms. Combining phase information from circadian and multidien IEA rhythms provides a novel biomarker for determining relative seizure risk with a large effect size in most subjects.
Angiotensin Blockade Inhibits Activation of Mitogen-Activated Protein Kinases in Rat Balloon-Injured Artery (1998)

Arterial JNKs and ERKs are dramatically activated by balloon injury associated with the activation of the AP-1 complex. These MAPK activations, followed by AP-1 activation, are mediated at least in part by the AT1 receptor. Thus, activation of JNKs and ERKs may be responsible for balloon injury-induced neointima formation.
Cognition and Depression: Current Status and Future Directions (2010)

Cognitive theories of depression posit that people's thoughts, inferences, attitudes, and interpretations, and the way in which they attend to and recall information, can increase their risk for depression. Three mechanisms have been implicated in the relation between biased cognitive processing and the dysregulation of emotion in depression: inhibitory processes and deficits in working memory, ruminative responses to negative mood states and negative life events, and the inability to use positive and rewarding stimuli to regulate negative mood. In this review, we present a contemporary characterization of depressive cognition and discuss how different cognitive processes are related not only to each other, but also to emotion dysregulation, the hallmark feature of depression. We conclude that depression is characterized by increased elaboration of negative information, by difficulties disengaging from negative material, and by deficits in cognitive control when processing negative information. We discuss treatment implications of these conclusions and argue that the study of cognitive aspects of depression must be broadened by investigating neural and genetic factors that are related to cognitive dysfunction in this disorder. Such integrative investigations should help us gain a more comprehensive understanding of how cognitive and biological factors interact to affect the onset, maintenance, and course of depression.
Suppression of mode partition noise by laser diode light injection (1982)

This paper describes the improvement in mode partition noise characteristics when a laser light is injected into a laser diode modulated at 400 Mbits/s. A single-mode fiber transmission experiment is carried out for the 1.5 μm region. A 20 km repeater spacing at 400 Mbit/s modulation is achieved by LD light injection. The center longitudinal mode power is increased to 94 percent of the total modes. Relative noise in the center longitudinal mode is improved 30 dB by optical injection of -18.2 dBm. However, the mode partition noise generated by noninjected modes is not completely suppressed. The relationship between the half-power width of the spectral envelope and signal-to-noise ratio (SNR) degradation is obtained at 20 km fiber length. If 3 dB excess SNR degradation is allowed for the mode partition noise, then the necessary half-power width of the spectral envelope is less than 0.6 nm.
Regulation of Insulin-Like Growth Factor I (IGF-I) Bioactivity in Vivo: Further Characterization of an IGF-I-Enhancing Antibody (1998)

We have previously demonstrated the ability of a polyclonal antibody raised against human insulin-like growth factor I (IGF-I) to potentiate, rather than inhibit, the growth-promoting activity of IGF-I. The anti-IGF-I Ig had a modest affinity for IGF-I, protected IGF-I from degradation, and reduced the IGF-I clearance rate while allowing efficient transfer of peptide from the circulation, leading to the suggestion that the antiserum might be behaving in an analogous manner to enhancing IGF-binding proteins (IGFBPs). The purpose of these studies was to investigate further the characteristics of this antiserum as a means of assessing the importance of IGF-I associated with circulating high mol wt IGFBPs to serve as a bioavailable reservoir of IGF-I peptide. 1) Epitope scanning using sequential and overlapping peptides spanning the entire length of IGF-I revealed one major linear region of anti-IGF-I Ig binding to IGF-I comprising the C-terminal region of the C-domain and the N-terminal region of the A-domain (Arg36-Ile43), a region not associated with receptor or IGFBP binding. 2) The fact that the antibody could potentiate IGF-I whether administered as a preincubated complex or separately indicated that complex formation could occur in the presence of IGFBPs in vivo. 3) The ability of the antibody to attenuate the acute hypoglycemic actions of IGF-I and LR3IGF-I was assessed by pretreating dwarf rats with either anti-IGF-I Ig or nonimmune Ig; 1 h after sc administration of peptide, plasma glucose levels decreased by about 4 mm (P < 0.001) in rats pretreated with nonimmune Ig. The duration of hypoglycemia was more prolonged in the LR3IGF-I-treated rats (P < 0.01). Neither IGF-I or LR3IGF-I induced any decrease in circulating glucose concentrations in the rats pretreated with the anti-IGF-I Ig, suggesting that the antibody gave protection against inappropriate acute IGF-induced hypoglycemia. 4) The potentiating effects of the anti-IGF-I Ig on the anabolic actions of IGF-I and LR3IGF-I were compared in dwarf mice. The anti-IGF-I Ig potentiated the increase in whole body weight gain induced by IGF-I by over 3-fold (P < 0.001), but did not change the anabolic action of LR3IGF-I despite its ability to double circulating levels of both IGF peptides. It is, therefore, possible that part of the mechanism of action of the anti-IGF-I Ig involves transfer of IGF-I to smaller mol wt binding proteins. These data confirm the potential of IGFBP-associated IGF-I to act as a reservoir of peptide and to regulate IGF-I activity in vivo.
B7-H3 is Overexpressed in Patients Suffering Osteosarcoma and Associated with Tumor Aggressiveness and Metastasis (2013)

B7-H3 is a member of the B7-family of co-stimulatory molecules, which has been shown to be broadly expressed in various tumor tissues, and which plays an important role in adaptive immune responses. The role of B7-H3 in osteosarcoma, however, remains unknown. In this study we used immunohistochemistry to analyze B7-H3 expression in 61 primary osteosarcoma tissues with case-matched adjacent normal tissues, and 37 osteochondroma and 20 bone fibrous dysplasia tissues. B7-H3 expression was expressed in 91.8% (56/61) of the osteosarcoma lesions, and the intensity of B7-H3 expression in osteosarcoma was significantly increased compared with adjacent normal tissues, osteochondroma and bone fibrous dysplasia tissues (p<0.001). Patients with high tumor B7-H3 levels had a significantly shorter survival time and recurrence time than patients with low tumor B7-H3 levels (p<0.001). Moreover, tumor B7-H3 expression inversely correlated with the number of tumor-infiltrating CD8(+) T cells (p<0.05). In vitro, increasing expression of B7-H3 promotes osteosarcoma cell invasion, at least in part by upregulating matrix metalloproteinase-2 (MMP-2). In conclusion, our study provides the first evidence of B7-H3 expression in osteosarcoma cells as a potential mechanism controlling tumor immunity and invasive malignancy, and which is correlated with patients' survival and metastasis.
Characterization of the Cross-Linked Structure of Hydrogels (2019)

The theoretical study of a hydrogel network has the purpose of revealing the structure and configuration of its chains by use of appropriate theoretical models. Characterization of the hydrogel network structure is a complex procedure because of the many types of possible networks, including, regular, irregular, loosely cross-linked, highly cross-linked, and imperfect networks. In order to determine the cross-linking density of a hydrogel, use is made of mainly two theories, the equilibrium swelling theory and the rubber elasticity theory. If an uncross-linked polymer is soluble in or thermodynamically compatible with a liquid penetrant, then the same polymer when cross-linked will be swollen by this liquid. When a cross-linked network acting as an elastomer is stretched, it reaches an equilibrium strain while the stress remains constant. The analysis of the cross-linked structure of hydrogels can be done by a variety of experimental techniques, prominent among which are swelling and mechanical tests.
Comprehensive Proteomics Analysis Reveals Metabolic Reprogramming of Tumor-Associated Macrophages Stimulated by the Tumor Microenvironment (2016)

Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. Although a role for TAMs in promoting tumor progression has been revealed, the differentiation mechanisms and intrinsic signals of TAMs regulated by the tumor microenvironment remain unclear. Here we constructed an in vitro TAMs cell model, TES-TAMs, which is from tumor-extract-stimulated bone-marrow-derived macrophages. We performed a comparative proteomics analysis of bone-marrow-derived macrophages and TES-TAMs, which indicated that TES-TAMs possessed characteristic molecular expression of TAMs. Intriguingly, the signal pathways enriched in up-regulated differentially expressed proteins of TAMs demonstrated that glycolysis metabolism reprogramming may play an important role in TAM differentiation. We found that hexokinase-2, a key mediator of aerobic glycolysis, and the downstream proteins PFKL and ENO1 were remarkably increased in both TES-TAMs and primary TAMs from our MMTV-PyMT mice model. This phenomenon was then verified in human THP-1 cell lines stimulated by tumor extract solution from breast cancer patient. Taken together, our study provides insight into the induction of TAM differentiation by the tumor microenvironment through metabolic reprogramming.
Prognostic Indicators for AIDS and Infectious Disease Death in HIV-Infected Injection Drug Users (1998)

In this study, plasma HIV-1 viral load independently and in combination with CD4+ cell count measurements provided powerful prognostic information for progression to AIDS and death caused by infectious disease in a population of predominantly African American IDUs. Combining categories of both markers provided a simple method for prognostically staging HIV disease.
Epigenetic Regulation of Foxp3 Expression in Regulatory T Cells by DNA Methylation (2009)

Abstract Foxp3, a winged-helix family transcription factor, serves as the master switch for CD4+ regulatory T cells (Treg). We identified a unique and evolutionarily conserved CpG-rich island of the Foxp3 nonintronic upstream enhancer and discovered that a specific site within it was unmethylated in natural Treg (nTreg) but heavily methylated in naive CD4+ T cells, activated CD4+ T cells, and peripheral TGFβ-induced Treg in which it was bound by DNMT1, DNMT3b, MeCP2, and MBD2. Demethylation of this CpG site using the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (Aza) induced acetylation of histone 3, interaction with TIEG1 and Sp1, and resulted in strong and stable induction of Foxp3. Conversely, IL-6 resulted in methylation of this site and repression of Foxp3 expression. Aza plus TGFβ-induced Treg resembled nTreg, expressing similar receptors, cytokines, and stable suppressive activity. Strong Foxp3 expression and suppressor activity could be induced in a variety of T cells, including human CD4+CD25− T cells. Epigenetic regulation of Foxp3 can be predictably controlled with DNMT inhibitors to generate functional, stable, and specific Treg.
Conversion of the E1A Cys4 zinc finger to a nonfunctional His2,Cys2 zinc finger by a single point mutation. (1991)

Trans-activation by the adenovirus E1A 289R protein requires a zinc finger defined by Cys-154, Cys-157, Cys-171, and Cys-174. Whereas individually replacing the four cysteine residues with serines resulted in a loss of transactivation, only three of the Cys----Ser mutants (C157S, C171S, and C174S) lost the ability to bind Zn(II). X-ray absorption fine structure analysis revealed that, in the wild-type protein, Zn(II) is coordinated by four cysteine residues whereas in the C154S mutant, Zn(II) is coordinated by two histidines and two cysteines. The mutant protein probably retains, as ligands, two cysteines on the right side of the zinc finger (Cys-171 and Cys-174) and recruits two of the four histidines on the left side (His-149, His-152, His-158, and His-160), despite the presence of Cys-157. This finding may shed light on the general structural requirements of zinc fingers.
Pathways to Diabetic Limb Amputation: Basis for Prevention (1990)

We defined the causal pathways responsible for 80 consecutive initial lower-extremity amputations to an extremity in diabetic patients at the Seattle Veterans Affairs Medical Center over a 30-mo interval from 1984 to 1987. Causal pathways, either unitary or composed of various combinations of seven potential causes (i.e., ischemia, infection, neuropathy, faulty wound healing, minor trauma, cutaneous ulceration, gangrene), were determined empirically after a synthesis by the investigators of various objective and subjective data. Estimates of the proportion of amputations that could be ascribed to each component cause were calculated. Twenty-three unique causal pathways to diabetic limb amputation were identified. Eight frequent constellations of component causes resulted in 73% of the amputations. Most pathways were composed of multiple causes, with only critical ischemia from acute arterial occlusions responsible for amputations as a singular cause. The causal sequence of minor trauma, cutaneous ulceration, and wound-healing failure applied to 72% of the amputations, often with the additional association of infection and gangrene. We specified precise criteria in the definition of causal pathway to permit estimation of the cumulative proportion of amputations due to various causes. Forty-six percent of the amputations were attributed to ischemia, 59% to infection, 61% to neuropathy, 81% to faulty wound healing, 84% to ulceration, 55% to gangrene, and 81% to initial minor trauma. An identifiable and potentially preventable pivotal event, in most cases an episode involving minor trauma that caused cutaneous injury, preceded 69 of 80 amputations. Defining causal pathways that predispose to diabetic limb amputation suggests practical interventions that may be effective in preventing diabetic limb loss.
[Observation on morphology and histology of Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. var. formosana (Boiss.) Shan et Yuan in the process of in vitro cultivation and polyploid induction]. (2000)

Induction treatment can be used as an effective biotechnological approach to adventitious buds in the process of tissue cultivation.
Single-shot two-photon exposure of commercial photoresist for the production of three-dimensional structures (1998)

We report the use of an amplified femtosecond laser for single-shot two-photon exposure of the commercial photoresist SU-8. By scanning of the focal volume through the interior of the resist, three-dimensional (3-D) structures are fabricated on a shot-by-shot basis. The 800-nm two-photon exposure and damage thresholds are 3.2 and 8.1TW/cm(2), respectively. The nonlinear nature of the two-photon process allows the production of features that are smaller than the diffraction limit. Preliminary results suggest that Ti:sapphire oscillators can achieve single-shot two-photon exposure with thresholds as low as 1.6TW/cm(2) at 700 nm, allowing 3-D structures to be constructed at megahertz repetition rates.
Efficient recovery of ENU-induced mutations from the zebrafish germline. (1994)

We studied the efficiency with which two chemical mutagens, ethyl methanesulfonate (EMS) and N-ethyl-N-nitrosourea (ENU) can induce mutations at different stages of spermatogenesis in zebrafish (Brachydanio rerio). Both EMS and ENU induced mutations at high rates in post-meiotic germ cells, as indicated by the incidence of F1 progeny mosaic for the albino mutation. For pre-meiotic germ cells, however, only ENU was found to be an effective mutagen, as indicated by the frequencies of non-mosaic mutant progeny at four different pigmentation loci. Several mutagenic regimens that varied in either the number of treatments or the concentration of ENU were studied to achieve an optimal ratio between the mutagenicity and toxicity. For the two most mutagenic regimens: 4 x 1 hr in 3 mM ENU and 6 x 1 hr in 3 mM ENU, the minimum estimate of frequencies of independent mutations per locus per gamete was 0.9-1.3 X 10(-3). We demonstrate that embryonic lethal mutations induced with ENU were transmitted to offspring and that they could be recovered in an F2 screen. An average frequency of specific-locus mutations of 1.1 X 10(-3) corresponded to approximately 1.7 embryonic lethal mutations per single mutagenized genome. The high rates of mutations achievable with ENU allow for rapid identification of large numbers of genes involved in a variety of aspects of zebrafish development.
CGH2466, a combined adenosine receptor antagonist, p38 mitogen‐activated protein kinase and phosphodiesterase type 4 inhibitor with potent in vitro and in vivo anti‐inflammatory activities (2005)

Theophylline, a phosphodiesterase inhibitor and adenosine receptor antagonist, is used in asthma and chronic obstructive pulmonary disease (COPD) treatment. However, the relatively low effectiveness of theophylline have recently led to reduced usage. The goal of the present study was to identify a theophylline-like compound with improved effectiveness. We discovered CGH2466, which not only antagonised the adenosine A1, A2b and A3 receptors with IC50 values of 19 +/- 4, 21 +/- 3 and 80 +/- 14 nM, respectively, but also inhibited the p38 mitogen-activated protein (MAP) kinases alpha and beta and the phosphodiesterase 4D (PDE4D) isoenzyme with IC50 values of 187 +/- 18, 400 +/- 38 and 22 +/- 5 nM, respectively. Despite similar potencies on individual targets, CGH2466 inhibited the production of cytokines and oxygen radicals by human peripheral blood leucocytes in vitro, more potently (IC50 values between 30 and 50 nM) than the standard p38 MAP kinase inhibitor SB203580 (30 nM to >1 microM), the PDE4 inhibitor cilomilast (120-400 nM) and the broad spectrum adenosine receptor antagonist CGS15943 (>10 microM). When given either orally or locally into the lungs, CGH2466 (3 to 10 mg kg(-1)) inhibited the ovalbumin- or lipopolysaccharide-induced airway inflammation in mice more potently than the single receptor antagonists or enzyme inhibitors used alone. In conclusion, CGH2466 through its combined activities at multiple targets exerted a powerful anti-inflammatory effect and therefore may have beneficial therapeutic value in diseases such as asthma and COPD.
Epigenetic silencing of claudin‐6 promotes anchorage‐independent growth of breast carcinoma cells (2007)

Cancer cells often exhibit loss of functional tight junctions (TJ), and disruption of the TJ structure is associated with cancer development. However, whether loss of a certain type of claudin, an integral membrane protein of TJ, is involved in malignant phenotypes remains to be clarified. Based on a report that claudin-6 functions as a tumor suppressor for breast cancer, the authors show here that suppression of claudin-6 expression results in increased resistance to various apoptogens, and causally enhances anchorage-independent growth properties. Because claudin-6 expression is partially silenced by promoter CpG island hypermethylation in MCF7 breast carcinoma cells, a synergistic effect of a demethylator and histone deacetylase inhibitor up-regulates the expression of endogenous claudin-6, which is sufficient for apoptotic sensitization and abrogation of colony-forming efficacy. In addition, decreased expression of claudin-6 promotes cellular invasiveness and transendothelial migration, accompanied by an increase in matrix metalloproteinase activity. These data suggest that the methylator phenotype of claudin-6 may at least partially contribute to enhanced tumorigenic and invasive properties of breast carcinoma cells.
SYNTHESIS AND SWELLING DEPENDENT ENZYMATIC DEGRADATION OF BORAX MODIFIED GUAR GUM FOR COLONIC DELIVERY PURPOSES (1995)

La gomme guar est un polysaccharide naturel faiblement soluble dans l'eau couramment employe comme agent epaississant dans les industries alimentaire et pharmaceutique. En tant qu'adjuvant pharmaceutique, elle peut etre utilisee pour une liberation specifique au niveau du colon car sa degradation au niveau du gros intestin humain a ete rapportee. Dans ce travail, la gomme guar est employee comme modele a partir duquel on recherche si les proprietes d'absorption de liquide peuvent etre augmentees par modification chimique afin d'accroitre sa degradation enzymatique. La gomme guara ete traitee par des proposions croissantes de borax, et les proprietes des nouveaux polymeres ont ete etudiees par mesure de la viscosite avant sechage, absorption atomique, spectroscopie infrarouge a transformee de Fourier et determination de la solubilite dans l'eau et d'absorption d'eau a l'equilibre. Il apparait que, malgre le traitement par le borax, la gomme guar (sous forme de film comme sous forme de comprimes) conserve la possibilite d'etre degradee par la galactomannanase. Les produits modifies ont un meilleur gonflement et, de ce,,ait, une meilleure degradation enzymatique. L'augmentation de la biodegradation des polymeres est directement proportionnelle a l'augmentation de leur capacite d'absorption de liquide