Miracle-dz/UniFAR-FTUs huggingface dataset:
Purification, Characterization, and Submitochondrial Localization of a 58-Kilodalton NAD(P)H Dehydrogenase

An NADH dehydrogenase activity from red beet (Beta vulgaris L.) root mitochondria was purified to a 58-kD protein doublet. An immunologically related dehydrogenase was partially purified from maize (Zea mays L. B73) mitochondria to a 58-kD protein doublet, a 45-kD protein, and a few other less prevalent proteins. Polyclonal antibodies prepared against the 58-kD protein of red beet roots were found to immunoprecipitate the NAD(P)H dehydrogenase activity. The antibodies cross-reacted to similar proteins in mitochondria from a number of plant species but not to rat liver mitochondrial proteins. The polyclonal antibodies were used in conjunction with maize mitochondrial fractionation to show that the 58-kD protein was likely part of a protein complex loosely associated with the membrane fraction. A membrane-impermeable protein cross-linking agent was used to further show that the majority of the 58-kD protein was located on the outer surface of the inner mitochondrial membrane or in the intermembrane space. Analysis of the cross-linked 58-kD NAD(P)H dehydrogenase indicated that specific proteins of 64, 48, and 45 kD were cross-linked to the 58-kD protein doublet. The NAD(P)H dehydrogenase activity was not affected by ethyleneglycol-bis([beta]-aminoethyl ether)-N,N[prime] -tetraacetic acid or CaCl2, was stimulated somewhat (21%) by flavin mononucleotide, was inhibited by p-chloromercuribenzoic acid (49%) and mersalyl (40%), and was inhibited by a bud scale extract of Platanus occidentalis L. containing platanetin (61%).
Bit-Interleaved LDPC-Coded Modulation with Iterative Demapping and Decoding

Bit-interleaved coded modulation (BICM) is a sub- optimal scheme from the average mutual information (AMI) point of view due to independent demapping. However, this AMI loss can be neglected for signal constellations with Gray mapping at high coding rates. AMI of amplitude-phase shift keying (APSK) constrained additive white Gaussian noise (AWGN) channel is provided in this paper, which shows that the BICM scheme has considerable loss with APSK constellations since no Gray mapping exists. Bit-interleaved low-density parity-check (LDPC) coded modulation (BILCM) is an excellent scheme and has been employed in many broadcasting and communication systems, however, such scheme also suffers from the independent demapping loss. Therefore, BILCM with iterative demapping and decoding (BILCM-ID) is proposed in this paper to overcome such loss. Simulation results show that the BILCM-ID scheme outweighs BILCM scheme by about 0.5 and 0.3 dB over AWGN channel for 32-APSK constellation at coding rates 2/3 and 4/5, respectively.
Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics

ABSTRACT Introduction: Second-generation antipsychotics (SGAs) are frequently co-prescribed with drug metabolic inducers and inhibitors. SGA pharmacokinetic drug-drug interactions (DDIs) with inducers and inhibitors have not received enough attention in the literature but can be studied in by using therapeutic drug monitoring (TDM). Areas covered: The limited information available on oral SGA pharmacokinetic DDIs is reviewed. A systematic literature search on the available oral SGA TDM studies is completed. By integrating TDM studies with the information on in vitro metabolism studies, case report/series and prospective studies, a table is provided to manage average SGA patients taking inducers or inhibitors by using TDM and/or dose SGA changes. Adding an inhibitor or discontinuing an inducer may increase plasma concentrations and cause adverse drug reactions (ADRs) on clozapine or risperidone. Quetiapine and lurasidone, which are very sensitive to decreases of plasma concentrations by induction, should not be administered with potent inducers. Prescribing sertindole with TDM may make its use safer. Expert opinion: Reading our article may encourage: 1) clinicians using these combinations to publish TDM case reports/series to demonstrate whether our dose indications are correct or not, in their patients with DDIs; and 2) pharmacokinetic researchers to study these DDIs in prospective and retrospective ways using large TDM databases.
Crohn's disease in Stockholm County during 1990-2001: an epidemiological update.

AIM To further assess of the incidence and localization of Crohn's disease (CD) in a well-defined population during the 1990s and to evaluate the prevalence of CD on the 1st of January 2002. METHODS In a retrospective population based study, all 16-90 years old citizens of Stockholm County diagnosed as having CD according to Lennard Jones' criteria between 1990 and 2001 were included. Case identification was made by using computerized inpatient and outpatient registers. Moreover private gastroenterologists were asked for possible cases. The extent of the disease and the frequency of anorectal fistulae were determined as were the ages at diagnosis. Further, the prevalence of CD on the 1(st) of January 2002 was assessed. RESULTS All the 1 389 patients, 689 men and 700 women, fulfilled the criteria for CD. The mean incidence rate for the whole period was 8.3 per 10(5) (95%CI 7.9 -8.8). There was no difference between the genders. The mean annual incidence of the whole study period for colorectal disease and ileocecal disease, was 4.4 (95%CI 4.0-4.7) and 2.4 (95%CI 2.1-2.6) per 10(5), respectively. Perianal disease occurred in 13.7% (95%CI 11.9-15.7 %) of the patients. The prevalence of CD was 213 per 100,000 inhabitants. CONCLUSION The incidence of CD has markedly increased during the last decade in Stockholm County and 0.2% of the population suffers from CD. The increase is attributed to a further increase of colorectal disease, while the incidence of ileocecal disease has remained stable.
Is tail vein injection a relevant breast cancer lung metastasis model?

BACKGROUND TWO MOST COMMONLY USED ANIMAL MODELS FOR STUDYING BREAST CANCER LUNG METASTASIS ARE: lung metastasis after orthotopic implantation of cells into the mammary gland, and lung implantations produced after tail vein (TV) injection of cells. Tail vein injection can produce lung lesions faster, but little has been studied regarding the differences between these tumors, thus, we examined their morphology and gene expression profiles. METHODS Syngeneic murine mammary adenocarcinoma, 4T1-luc2 cells, were implanted either subcutaneously (Sq), orthotopically (OS), or injected via TV in Balb/c mice. Genome-wide microarray analyses of cultured 4T1 cells, Sq tumor, OS tumor, lung metastases after OS (LMet), and lung tumors after TV (TVt) were performed 10 days after implantation. RESULTS Bioluminescence analysis demonstrated different morphology of metastases between LMet and TVt, confirmed by histology. Gene expression profile of cells were significantly different from tumors, OS, Sq, TVt or LMet (10,350 probe sets; FDR≤1%; P<0.0001). Sq tumors were significantly different than OS tumors (700 probe sets; FDR≤15%; P<0.01), and both tumor types (Sq and OS) were significantly different than LMet (1,247 probe sets; >1.5-fold-change; P<0.01), with no significant difference between TVt and LMet. CONCLUSIONS There were significant differences between the gene profiles of cells in culture and OS versus LMet, but there were no differences between LMet versus TVt. Therefore, the lung tumor generated by TVt can be considered genetically similar to those produced after OS, and thus TVt is a relevant model for breast cancer lung metastasis.
Increased sympathetic activity in rats submitted to chronic intermittent hypoxia

Long‐term exposure to intermittent hypoxia may lead to important cardiovascular dysfunctions, such as hypertension. Rodent models of chronic intermittent hypoxia (CIH) have been used to study the mechanisms underlying the increase in mean arterial pressure (MAP) observed after exposure to CIH. Several studies suggest that the hypertension of rats submitted to CIH is associated with an increase in sympathetic activity. However, there are no studies documenting the direct measurement of sympathetic activity in conscious freely moving rats exposed to CIH. Therefore, the present study aimed to evaluate whether or not the increase of MAP in rats exposed to CIH is associated with an increase in sympathetic activity. To reach this goal, we analysed the effect of ganglionic blockade on baseline MAP as well as the plasma levels of catecholamines. Rats submitted to CIH (fractional inspired O2 of 6%, for 40 s in every 9 min, 8 h day−1) for 35 days (n= 31) exhibited a significant increase in MAP compared with control rats (n= 28) maintained under normoxia (112 ± 2 versus 103 ± 1 mmHg, P= 0.0003). The injection of the ganglionic blocker hexamethonium resulted in a similar fall in MAP in CIH and control groups (−46 ± 2 versus−41 ± 3 mmHg). However, hexamethonium after previous antagonism of the angiotensin II type 1 (AT1) receptors with losartan produced a larger decrease in MAP in the CIH than in the control group (−58 ± 2 versus−50 ± 2 mmHg, P= 0.0165). The injection of losartan itself produced no major changes in the baseline MAP in both groups. The measurement of plasma catecholamines showed an increase in plasma noradrenaline (10.12 ± 0.90 versus 4.74 ± 0.32 ng ml−1, P= 0.0042) in rats exposed to CIH compared with control rats. These data provide strong evidence to support the concept that rats submitted to CIH exhibit an increase in sympathetic activity, which seems to be determinant in the maintenance of hypertension in this experimental model.
Depression is associated with some patient‐perceived cosmetic changes, but not with radiotherapy‐induced late toxicity, in long‐term breast cancer survivors

Although depression is prevalent in long‐term breast cancer survivors (LTBCS; ≥5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS.
Comparison of neurobehavioral function in workers exposed to a mixture of organic and inorganic lead and in workers exposed to solvents.

The neurobehavioral effects of lead (organic and inorganic) and organic solvents were compared in 386 U.S. workers (52 reference, 190 lead, and 144 solvent workers). The association between neurobehavioral test performance and duration of exposure to lead or solvents was also examined and compared. The neurobehavioral test battery consisted of examiner and computer-administered neurobehavioral tests, a test of olfactory function, and questionnaires that assessed neuropsychiatric symptoms. Adjusted mean differences on the neurobehavioral test scores were estimated by comparing the exposed group to the referent group using linear regression and adjusting for premorbid intellectual ability, age, and race. Both lead and solvents were associated with diminished neurobehavioral performance in all neurobehavioral areas tested. Specifically, while lead and solvent exposure had the same magnitude of adverse effects on tests of manual dexterity, lead exposure was associated with greater adverse effects on memory and learning tests but with less adverse effects on executive/motor tests and on a test of olfaction than solvent exposure. An elevated number of neuropsychiatric symptoms was reported by 7% of the referent group, 43% of the lead group, and 15% of the solvent group. For exposure duration of < or = 10 years, more neurobehavioral decrements were found in the solvent group relative to the lead group. However, for exposure duration of > or = 18 years, the lead group showed more decrements than the solvent group. Overall, these data suggest differences in neurobehavioral functioning between the lead (organic and inorganic) and solvent exposed workers examined in this study.
Growing School Leaders: An Exploration of Perceptions, Actions, and Support following a Formative Assessment Experience

The National Association of Secondary School Principals’ Selecting and Developing the 21st Century Principal program is a formative assessment identifying skills linked to effective leadership, and it is based on a simulation designed to replicate a school principal's day. The Long Island School Leadership Center became a site for this program in 2006. Using data generated from a sample of the center's participants, this mixed methods study examined (1) how participants scored on the assessment and to what extent they found it accurate and helpful, (2) the types and levels of professional development follow-up activities participants pursued, and (3) the types and levels of support they received. The findings highlighted that the assessment results proved to be an impetus for action with participants creating a specific plan to further leadership development or by heightening their self-awareness that prompted behavioral changes. The professional development activities of choice were aligned with job-related skills or had the potential to promote advancement, and participants particularly valued ongoing internal administrative support. In a few cases, the combination of identified skills based on assessment performance, coupled with targeted professional development and supported by in-district mentors, accelerated the participant's growth. In this light, this exploratory study forms the basis for further investigations of the nexus of formative assessment, professional development, and support for school administrators.
Inhibitory Effect of 12-O-Tetradecanoylphorbol-13-acetate Alone or in Combination with All-trans-Retinoic Acid on the Growth of LNCaP Prostate Tumors in Immunodeficient Mice

Clinically achievable concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA; 0.16–0.32 nm) and all-trans-retinoic acid (ATRA; 0.5–1 μm) had a synergistic inhibitory effect on the growth of cultured LNCaP prostate cancer cells, and apoptosis was markedly stimulated. In additional studies, NCr immunodeficient mice received s.c. injection with LNCaP cells in Matrigel. After 4–6 weeks, mice with well-established tumors received i.p. injection with vehicle, TPA (0.16 nmol/g body weight), ATRA (0.5 nmol/g body weight), or TPA+ATRA in vehicle once a day for 46 days. Tumor growth occurred in all of the vehicle-treated control mice. The percentage of animals with some tumor regression after 21 days of treatment was 0% for the control group, 31% for the ATRA group, 62% for the TPA group, and 100% for the TPA+ATRA group (13 mice/group). Although treatment of the mice with TPA or TPA+ATRA continued to inhibit tumor growth for the duration of the 46-day study, treatment of the mice with ATRA alone did not inhibit tumor growth beyond 28 days of daily injections (6 mice/group). Mechanistic studies indicated that treatment of the mice with TPA or TPA+ATRA for 46 days increased apoptosis in the tumors, and treatment with TPA+ATRA also decreased the mitotic index. Because the dose of TPA used in this study was effective and resulted in clinically achievable blood levels, clinical trials with TPA alone or in combination with ATRA in patients with prostate cancer may be warranted.
Salicylic acid enhances antifungal resistance to Magnaporthe grisea in rice plants

Salicylic acid (SA) may play an important role in induced disease resistance in rice but its mode of action in plant defence remains unclear. In this study,we examined the effect of exogenous SA treatment on host resistance and biochemistry of four near-isogenic lines of rice to the blast fungus Magnaporthe grisea. Host resistance, as indicated by suppressed blast lesion formation, was enhanced following foliar application of 8 mM SA in the two isogenic lines susceptible to the pathogen. Exogenous SA treatment increased the enzyme activity of peroxidase and polyphenol oxidase in all isogenic lines. Chemical analysis of crude leaf extracts detected higher concentrations of four rice phytoalexins (oryzalexin A, C and F and momilactone A) following root application of SA treatment. Furthermore, the hydrolysates of conjugated antifungal compounds from the SA-treated rice showed a much more potent inhibitory effect on the spore germination of M. grisea than the controls from the untreated plants, suggesting the existence of inducible conjugated antifungal compounds. Taken together, these data demonstrate that exogenous SA treatment of rice could increase production of the enzymes implicated in resistance to oxidative stresses and antifungal compounds, which appear to play a significant role in rice resistance to the invasion of blast fungal pathogens.
From mouth to hand: Gesture, speech, and the evolution of right-handedness

The strong predominance of right-handedness appears to be a uniquely human characteristic, whereas the left-cerebral dominance for vocalization occurs in many species, including frogs, birds, and mammals. Right-handedness may have arisen because of an association between manual gestures and vocalization in the evolution of language. I argue that language evolved from manual gestures, gradually incorporating vocal elements. The transition may be traced through changes in the function of Broca's area. Its homologue in monkeys has nothing to do with vocal control, but contains the so-called “mirror neurons,” the code for both the production of manual reaching movements and the perception of the same movements performed by others. This system is bilateral in monkeys, but predominantly left-hemispheric in humans, and in humans is involved with vocalization as well as manual actions. There is evidence that Broca's area is enlarged on the left side in Homo habilis, suggesting that a link between gesture and vocalization may go back at least two million years, although other evidence suggests that speech may not have become fully autonomous until Homo sapiens appeared some 170,000 years ago, or perhaps even later. The removal of manual gesture as a necessary component of language may explain the rapid advance of technology, allowing late migrations of Homo sapiens from Africa to replace all other hominids in other parts of the world, including the Neanderthals in Europe and Homo erectus in Asia. Nevertheless, the long association of vocalization with manual gesture left us a legacy of right-handedness.
Development and validation of a breast cancer risk prediction model for Thai women: a cross-sectional study.

BACKGROUND Breast cancer risk prediction models are widely used in clinical practice. They should be useful in identifying high risk women for screening in limited-resource countries. However, previous models showed poor performance in derived and validated settings. Therefore, we aimed to develop and validate a breast cancer risk prediction model for Thai women. MATERIALS AND METHODS This cross-sectional study consisted of derived and validation phases. Data collected at Ramathibodi and other two hospitals were used for deriving and externally validating models, respectively. Multiple logistic regression was applied to construct the model. Calibration and discrimination performances were assessed using the observed/expected ratio and concordance statistic (C-statistic), respectively. A bootstrap with 200 repetitions was applied for internal validation. RESULTS Age, menopausal status, body mass index, and use of oral contraceptives were significantly associated with breast cancer and were included in the model. Observed/expected ratio and C-statistic were 1.00 (95% CI: 0.82, 1.21) and 0.651 (95% CI: 0.595, 0.707), respectively. Internal validation showed good performance with a bias of 0.010 (95% CI: 0.002, 0.018) and C-statistic of 0.646(95% CI: 0.642, 0.650). The observed/expected ratio and C-statistic from external validation were 0.97 (95% CI: 0.68, 1.35) and 0.609 (95% CI: 0.511, 0.706), respectively. Risk scores were created and was stratified as low (0-0.86), low-intermediate (0.87-1.14), intermediate-high (1.15-1.52), and high-risk (1.53-3.40) groups. CONCLUSIONS A Thai breast cancer risk prediction model was created with good calibration and fair discrimination performance. Risk stratification should aid to prioritize high risk women to receive an organized breast cancer screening program in Thailand and other limited-resource countries.
The Role of Peers and Families in Predicting the Loneliness Level of Adolescents

Abstract The authors investigated the relative contribution of peer relations, family structure, and demographic variables in predicting loneliness in adolescents. Ninth-grade high school students (N = 756) from 8 different schools representing various socioeconomic status in Ankara, Turkey, completed the UCLA Loneliness Scale (D. Russell, L. A. Peplau, & M. L. Ferguson, 1978), the Family Structure Assessing Instrument (A. Gülerce, 1996), and an author-constructed questionnaire involving demographic information and variables on peer relations. Results of multiple regression analyses indicated that all three sets of variables accounted for 41% of the variance in loneliness scores. Additionally, peer relations contributed 34% of the variance, family structure 14%, and demographic variables 3%. Within the limits of the study, peer relations appear to be the best predictors of adolescent loneliness.
Dietary Human Milk Oligosaccharides but Not Prebiotic Oligosaccharides Increase Circulating Natural Killer Cell and Mesenteric Lymph Node Memory T Cell Populations in Noninfected and Rotavirus-Infected Neonatal Piglets.

Background: Human milk oligosaccharides (HMOs) have antimicrobial and immunomodulatory actions. It has previously been reported that these oligosaccharides contribute to the reduced duration of rotavirus-induced diarrhea in pigs.Objective: We measured the effects of HMOs and prebiotic oligosaccharides on immune cell populations from noninfected and rotavirus-infected pigs. We hypothesized that dietary HMOs would modulate systemic and gastrointestinal immunity.Methods: Colostrum-deprived newborn pigs were fed formula, formula with 4 g HMOs/L (2'-fucosyllactose, lacto-N-neotetraose, 6'-sialyllactose, 3'-sialyllactose, and free sialic acid), or formula with 3.6 g short-chain galactooligosaccharides/L and 0.4 g long-chain fructooligosaccharides/L. On day 10, half of the pigs were infected with the porcine rotavirus strain OSU. Peripheral blood mononuclear cell (PBMC), mesenteric lymph node (MLN), and ileal Peyer's patch immune cell populations were assessed with the use of flow cytometry 5 d postinfection. Interferon-γ (IFN-γ)-producing cells were assessed with the use of Enzyme-Linked ImmunoSpot assay.Results: Infection changed immune cell populations with more systemic natural killer (NK) cells, memory effector T cells, and major histocompatibility complex II+ cells in infected than noninfected pigs (P < 0.06). Regardless of infection status, HMO-fed pigs had nearly twice as many PBMC NK cells, 36% more MLN effector memory T cells, and 5 times more PBMC basophils than formula-fed pigs (P < 0.04). These populations were intermediate in pigs fed prebiotics. PBMCs from HMO-fed noninfected pigs had twice as many IFN-γ-producing cells as did those from formula-fed noninfected pigs (P = 0.017). The PBMCs and MLNs of formula-fed noninfected pigs had 3 times more plasmacytoid dendritic cells (pDCs) than those of HMO-fed noninfected and formula-fed infected pigs (P < 0.04). In the MLNs, the formula-fed noninfected pigs had more macrophages, pDCs, and mature DCs (P < 0.04) but fewer immature DCs than HMO-fed noninfected pigs (P = 0.022). Conclusions: Dietary HMOs were more effective than prebiotics in altering systemic and gastrointestinal immune cells in pigs. These altered immune cell populations may mediate the effects of dietary HMOs on rotavirus infection susceptibility.