Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemical coding of the human gastrointestinal nervous system: Cholinergic, VIPergic, and catecholaminergic phenotypes

The aim of this investigation was to identify the proportional neurochemical codes of enteric neurons and to determine the specific terminal fields of chemically defined nerve fibers in all parts of the human gastrointestinal (GI) tract. For this purpose, antibodies against the vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), dopamine β‐hydroxylase (DBH), serotonin (5‐HT), vasoactive intestinal peptide (VIP), and protein gene product 9.5 (PGP 9.5) were used. For in situ hybridization 35S‐labeled VMAT1, VMAT2, and VAChT riboprobes were used. In all regions of the human GI tract, 50–70% of the neurons were cholinergic, as judged by staining for VAChT. The human gut unlike the rodent gut exhibits a cholinergic innervation, which is characterized by an extensive overlap with VIPergic innervation. Neurons containing VMAT2 constituted 14–20% of all intrinsic neurons in the upper GI tract, and there was an equal number of TH‐positive neurons. In contrast, DBH was absent from intrinsic neurons. Cholinergic and monoaminergic phenotypes proved to be completely distinct phenotypes. In conclusion, the chemical coding of human enteric neurons reveals some similarities with that of other mammalian species, but also significant differences. VIP is a cholinergic cotransmitter in the intrinsic innervation of the human gut. The substantial overlap between VMAT2 and TH in enteric neurons indicates that the intrinsic catecholaminergic innervation is a stable component of the human GI tract throughout life. The absence of DBH from intrinsic catecholaminergic neurons indicates that these neurons have a dopaminergic phenotype. J. Comp. Neurol. 459:90–111, 2003. © 2003 Wiley‐Liss, Inc.
Measuring Business Cycle Time

The business cycle analysis of Burns and Mitchell and the National Bureau of Economic Research presumed that aggregate economic variables evolve on a time scale defined by business cycle turning points rather than by months or quarters. Do macroeconomic variables appear to evolve on an economic rather than a calendar time scale? Evidence presented here suggests that they do. However, the estimated economic time scales are only weakly related to business cycle time scales, providing evidence against the view underlying traditional business cycle analysis.
Smoking Cessation and Associated Risk of Metabolic Syndrome in Women

Evaluation of: Kwasniewska M, Pikala M, Kaczmarczyk-Chalas K et al. Smoking status, the menopausal transition, and metabolic syndrome in women. Menopause 19, 194–201 (2012). This study was a cross-sectional analysis of 7462 randomly selected Polish women, aged 20–74 years, who had completed the WOBASZ, a Polish National Multicenter Health Survey. Components of metabolic syndrome, including waist circumference, fasting plasma glucose, triglycerides, blood pressure and high-density lipoprotein cholesterol were measured in addition to BMI. The authors assessed the prevalence of metabolic syndrome in pre- and postmenopausal women with respect to smoking status (current smoking, past smoking or never smoked). They determined that the prevalence of metabolic syndrome was 3.3-fold higher in postmenopausal women compared with premenopausal women and that past smoking was associated with higher odds of metabolic syndrome, regardless of menopausal status. Previous studies that have examined the risk of developing metabolic syndrome after smoking cessation did not assess menopausal status in women, and also used reported rather than measured anthropomorphic data. This study provides an additional perspective on the metabolic changes that may occur in women after smoking cessation.
Endocannabinoid function in hippocampal synaptic plasticity and spatial working memory

Cannabis has been used medicinally for millennia, but the cannabinoid (CB) field exploded with the identification of its endogenous receptors and endocannabinoids (eCBs). In vitro experimentation established that eCBs alter synaptic plasticity at presynaptic nerve terminals; however, the characterization of the eCB system (ECS) in vivo remains incomplete. This study aimed to determine the mechanism of in vivo eCB-mediated hippocampal synaptic plasticity and to analyze the effects this plasticity had on spatial working memory (SWM). With in vivo recordings of field excitatory postsynaptic potentials (fEPSPs) in anesthetized mice and rats as well as pharmacological manipulation of the ECS and glutamate receptor antagonism, it was found that eCBs, both anandamide (AEA) and 2-arachnidonyl glycerol (2-AG), caused LTD at hippocampal CA3-CA1 synapses. Induction of eCB-LTD occurs via a sequential activation of cannabinoid type-1 receptor (CB 1 R) and NR2B-containing NMDA receptor (NR2BR) and is expressed through the endocytosis of AMPA receptors (AMPARs). Increased eCB tone also caused an impairment of SWM for over 24 hours in the Delayed Non-Match-To-Sample (DNMTS) T-maze. This study provides the first evidence that an acute administration of eCB degradative enzyme inhibitors not only produces an in vivo LTD at hippocampal CA3-CA1 synapses that requires CB 1 R, NR2BR, and AMPAR, but also impairs SWM, a phenomenon also caused by an acute injection of exogenous CBs.
Identification of an 11S globulin as a major hazelnut food allergen in hazelnut-induced systemic reactions.

BACKGROUND Hazelnuts are a common cause of food allergy. Allergic reactions to hazelnuts range from oral allergy syndrome caused by cross-reactivity between tree pollen and hazelnut proteins to severe anaphylactic reactions. Little information is available regarding the identification of pollen-independent hazelnut allergens. OBJECTIVE The aim of the study was to identify these pollen-independent allergens in patients with hazelnut allergy with systemic reactions. METHODS Extracted hazelnut proteins were separated by means of 2-dimensional PAGE, and immunolabeling was performed with individual sera from 14 patients with hazelnut-induced systemic reactions. Edman sequencing was performed on a 40-kd protein identified as an allergen. In parallel, RNA isolated from hazelnuts was used to construct a cDNA library. By using the peptide sequence data, oligonucleotide primers were synthesized and used to screen the library. Full-length cDNA clones were isolated, sequenced, expressed, and screened with patient sera. RESULTS By using 2-dimensional proteomics, a protein fraction at 40 kd was recognized by serum IgE from 86% (12/14) of the patients with hazelnut allergy with systemic reactions. Two internal amino acid sequences were determined by means of Edman sequencing. Screening of the prepared hazelnut cDNA library with oligonucleotides based on these internal peptide sequences resulted in isolation of a novel protein cDNA. The new protein, named Cor a 9, belongs to the 11S globulin seed storage protein family. This family comprises known food allergens in peanut (Ara h 3) and soybean (glycine max). The pairwise homology among these 3 proteins ranges from 45% to 50%. Interestingly, one known IgE-binding epitope of Ara h 3 shares 67% of homologous amino acid residues with the corresponding area of Cor a 9. The amino acids that differ were previously shown not to be critical for IgE binding in Ara h 3. CONCLUSION Cor a 9 is the first tree pollen-unrelated hazelnut allergen isolated, sequenced, and cloned. The identification of food allergens is the first step toward generating recombinant allergens for use in future immunotherapeutic approaches. In addition, the detection of conserved IgE epitopes in common food allergens, such as seed storage proteins, might be a useful tool for predicting cross-reactivity to certain foods.
A confluence of epidemics: Does hepatitis C cause type 2 diabetes?

Hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. This relationship has not been investigated at the population level, and its biological mechanism remains unknown. OBJECTIVE: To examine the prevalence of type 2 diabetes among persons with HCV infection in a representative sample of the general adult population of the United States. DESIGN: Cross-sectional national survey. SETTING: The Third National Health and Nutrition Examination Survey, 1988-1994. PARTICIPANTS: 9841 persons older than 20 years of age for whom data on HCV infection and diabetes were complete. MEASUREMENTS: The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting plasma glucose measurement and medication history. Presence of HCV infection was assessed by testing for serum HCV-speciﬁc antibodies (anti-HCV). RE-SULTS: Of the 9841 persons evaluated, 8.4% had type 2 diabetes and 2.1% were anti-HCV positive. Type 2 diabetes occurred more often in persons who were older, were non-white, had a high body mass index, and had low socioeconomic status. Type 2 diabetes was less common in persons who acknowledged previous illicit drug use. After adjustment for these factors, persons 40 years of age or older with HCV infection were more than three times more likely than those without HCV infection to have type 2 diabetes (adjusted odds ratio, 3.77 [95% CI, 1.80 to 7.87]). None of the 19 persons with type 1 diabetes were anti-HCV positive. CONCLUSION: In the United States, type 2 diabetes occurs more often in persons with HCV infection who are older than 40 years of age.
Japan and the Changing Global Financial Order

The global financial system has been undergoing enormous structural changes in recent years. Not only have financial markets become integrated to a degree unparalleled in the post1945 period, but immense shifts are also under way in the underlying power positions of states. Although full European monetary and financial union will pose a serious threat to American financial hegemony in the near future, the more dramatic shift to date has been the growth in Japan's financial power. This essay addresses two issues associated with Japan's increased role in the world's financial system. The first section seeks to clarify the debate concerning the degree to which Japan's rise has undermined the financial hegemony of the United States. By putting Japan's current position in a long historical context, it is shown that Japan's financial influence has often been exaggerated. At the same time, however, there are strong reasons to believe that it will continue to grow in the coming years. The second section
Low-Power and High Performance Sinusoidal Clocked Dynamic Circuit Design

Important characteristic of any VLSI circuit is its power consumption, reliability, operating speed and silicon area. Dynamic CMOS designs provide high operating speeds compared to static CMOS designs combined with low silicon area requirements. Pipelines can be used for achieving high circuit operating speeds. However, as the operating frequency increases, the number of pipeline stages should also increase and so the memory elements. These memory elements increase the area overhead and restrict the maximum achievable frequency due to their delays. Memory-less pipelines based on dynamic design address these issues but, still require high power consumption for the clock signal. In this paper we propose a sinusoidal three-phase clocking scheme that reduces the power required by the clock and offers high circuit operating frequencies. Thus the proposed technique provides advantages over preexisting techniques in terms of power requirement, area of implementation and operating speed.
Pulmonary vascular responses to exercise: a haemodynamic observation

Exercise testing provides additional information over resting variables and is a standard of care in the assessment of coronary artery disease with less subsequent cardiovascular events. In pulmonary hypertension (PH), right ventricular function is clearly an important determinant of survival. However, right ventricular impairment is currently assessed only during resting conditions. Exercise (stress) testing may provide further insight into the complex paradigm of right ventricular dysfunction, right ventricular–left ventricular interdependence and right ventricular–pulmonary artery coupling. Whether pulmonary artery pressure ( P pa)–flow relationships during exercise provides a window into earlier diagnosis of functionally significant PH or adds incrementally to our armamentarium of diagnostic tests and prognostic indicators in PH, is a topic of ongoing investigation. In this issue of the European Respiratory Journal ( ERJ ), the studies by Kovacs et al. [1] and Whyte et al. [2] discuss the potential clinical utility of identifying “normal” and “abnormal” pulmonary vascular response patterns to exercise in patients aged ≤50 yrs. The clinical significance of a hypertensive P pa response to exercise is currently uncertain. It may reflect a normal variant without clinical significance, or it may reflect a bona fide cardiopulmonary limitation and abnormal phenotype. In support of the latter, asymptomatic relatives of individuals with established idiopathic or familial PH have demonstrated an abnormal response to exercise [3]. Few studies have used right heart catheterisation (RHC) to address whether mean P pa ( P pa) >30 mmHg during exercise represents an aberrant pulmonary vascular system in “at-risk” populations [4–11]. Recently, Tolle et al. [9] evaluated a large cohort with exertional dyspnoea who underwent simultaneous cardiopulmonary exercise testing (CPET) and RHC. At maximal exercise, P pa and pulmonary vascular resistance (PVR) were highest, while resting pulmonary arterial hypertension was lowest in …
Cell Type-Specific Firing during Ripple Oscillations in the Hippocampal Formation of Humans

High-frequency field ripples occur in the rodent hippocampal formation and are assumed to depend on interneuron type-specific firing patterns, structuring the activity of pyramidal cells. Ripples with similar characteristics are also present in humans, yet their underlying cellular correlates are still unknown. By in vivo recording interneurons and pyramidal cells in the human hippocampal formation, we find that cell type-specific firing patterns and phase-locking on a millisecond timescale can be distinguished during ripples. In particular, pyramidal cells fired preferentially at the highest amplitude of the ripple, but interneurons began to discharge earlier than pyramidal cells. Furthermore, a large fraction of cells were phase-locked to the ripple cycle, but the preferred phase of discharge of interneurons followed the maximum discharge probability of pyramidal neurons. These relationships between human ripples and unit activity are qualitatively similar to that observed in vivo in the rodents, suggesting that their underlying mechanisms are similar.
Overview of violence to self and others during the first episode of psychosis.

BACKGROUND We aimed to review the evidence for an association between the first episode of psychosis and violence and to consider the possible explanations for this association and the implications for clinicians and service providers. DATA SOURCES We searched for published studies in English describing an association between violence and first-episode psychosis using the subject headings, key words, abstracts, and titles in PubMed/MEDLINE from 1970 to 2010, using the terms first-episode schizophrenia OR first-episode psychosis OR early schizophrenia AND suicide OR self harm OR suicide attempt OR homicide OR violence. STUDY SELECTION We identified 20 studies reporting data on violent suicide attempts, self-mutilation, minor violence, severe nonlethal interpersonal violence, or homicide in first-episode and previously treated psychosis. DATA EXTRACTION The number of people committing acts of violence prior to initial treatment for psychosis and after initial treatment was extracted from the relevant studies. RESULTS The proportion of people found to be in the first episode of psychosis at the time of an act of violence was compared to the expected ratio of first-episode to previously treated patients. A substantial proportion of psychotic patients examined after violent suicide attempts (49%), major self-mutilation (54%), homicide (39%), and assault resulting in serious injury (38%) are in their first episode of psychosis. Moreover, a substantial proportion of first-episode patients commit an act of less serious violence or attempt suicide prior to initial treatment. CONCLUSIONS The findings support the need for early intervention and community-wide programs to reduce the duration of untreated psychosis.
Small Molecule Therapeutics MTI-101 ( Cyclized HYD 1 ) Binds a CD 44 Containing Complex and Induces Necrotic Cell Death in Multiple Myeloma

Our laboratory recently reported that treatment with the D-amino acid containing peptide HYD1 induces necrotic cell death in multiple myeloma cell lines. Because of the intriguing biological activity and promising in vivo activity of HYD1, we pursued strategies for increasing the therapeutic efficacy of the linear peptide. These efforts led to a cyclized peptidomimetic, MTI-101, with increased in vitro activity and robust in vivo activity as a single agent using two myeloma models that consider the bone marrow microenvironment. MTI-101 treatment similar to HYD1 induced reactive oxygen species, depleted ATP levels, and failed to activate caspase-3. Moreover, MTI-101 is cross-resistant in H929 cells selected for acquired resistance to HYD1. Here, we pursued an unbiased chemical biology approach using biotinylated peptide affinity purification and liquid chromatography/tandem mass spectrometry analysis to identify binding partners of MTI-101.Using this approach,CD44was identifiedas apredominant bindingpartner. Reducing the expression of CD44 was sufficient to induce cell death in multiple myeloma cell lines, indicating that multiple myeloma cells require CD44 expression for survival. Ectopic expression of CD44s correlated with increased binding of the FAM-conjugated peptide. However, ectopic expression of CD44s was not sufficient to increase the sensitivity to MTI-101–induced cell death. Mechanistically, we show that MTI-101–induced cell death occurs via a Rip1-, Rip3-, or Drp1-dependent and -independent pathway. Finally, we show that MTI-101 has robust activity as a single agent in the SCID-Hu bone implant and 5TGM1 in vivo model of multiple myeloma. Mol Cancer Ther; 12(11); 1–13. 2013 AACR.
Complexity Analysis of Unsaturated Flow in Heterogeneous Media Using a Complex Network Approach

In this study, we investigate the complexity of two-phase flow (air/water) in a heterogeneous soil sample by using a complex network theory . Based on the different similarity measurements (i.e., correlation, Euclidean metrics) over the emerged patterns from the evolution of saturation of non-wetting phase of a multi-heterogeneous soil sample, the emerged complex networks are recognized. Understanding of the properties of complex networks (such degree distribution, mean path length, clustering coefficient) can be supposed as a way to analysis of variation of saturation profiles structures (as the solution of finite element method on the coupled PDEs) where complexity is coming from the changeable connection and links between assumed nodes. Also, the path of evolution of the supposed system will be illustrated on the state space of networks either in correlation and Euclidean measurements. The results of analysis showed in a closed system the designed complex networks approach to a small world network where the mean path length and clustering coefficient are low and high, respectively. As another result, the evolution of macro -states of system (such mean velocity of air or pressure) can be scaled with characteristics of structure complexity of saturation. In other part, we tried to find a phase transition criterion based on the variation of non-wetting phase velocity profiles over a network which had been constructed over correlation distance.
Treatment of Visual Perceptual Deficits after Stroke: Single Case Studies on Four Patients with Right Hemiplegia

The transfer of training approach to the treatment of visual perceptual deficits was evaluated with four right hemiplegic stroke patients, using single-case experimental designs. The results showed little evidence of effective treatment for individual perceptual deficits. Perceptual stimulation alone may have produced some general improvements. The importance of perceptual assessment and the monitoring of progress is discussed.
Tuberculostearic acid in lymph nodes from patients with sarcoidosis.

It has earlier been suggested that mycobacteria may play an aetiological role in the development of sarcoidosis. To investigate this further we analyzed the presence of a characteristic mycobacterial constituent, tuberculostearic acid (TS, 10-methyloctadecanoic acid), in lymph nodes from 22 patients with sarcoidosis and in eleven children and three adult controls. To detect TS gas chromatography/mass spectrometry was used. These findings were compared with the results from conventional mycobacterial culture and radiometric respirometry. Although the latter techniques failed to detect mycobacteria in all the tested tissue samples, TS was found in various amounts. Thus, 0-3 micrograms TS/g freeze-dried tissue was noted in eight sarcoid patients, 3-50 micrograms TS/g in eight and 51-400 micrograms TS/g in the remaining six patients. Among the controls only 1/14 had detectable TS. In one patient with lymph node tuberculosis TS was in the range 51-400 micrograms/g. We conclude that the findings could be explained by the presence of mycobacteria not cultivable with the studied techniques or with the presence of remnants after an earlier colonisation with mycobacteria, e.g. BCG-vaccination. Mycobacteria or mycobacterial cell-envelope in sarcoid tissue may possibly act as cofactors in the development of the disease, i.e. they might function as triggering agents (adjuvans) of the immune response. On the other hand the findings may be without any aetiological significance. In that latter case a hitherto unknown lack of wax decomposition during several decades has to be considered.