Miracle-dz/UniFAR-FTUs huggingface dataset:
Determination of amide hydrogen exchange by mass spectrometry: A new tool for protein structure elucidation

A new method based on protein fragmentation and directly coupled microbore high‐performance liquid chromatography–fast atom bombardment mass spectrometry (HPLC‐FABMS) is described for determining the rates at which peptide amide hydrogens in proteins undergo isotopic exchange. Horse heart cytochrome c was incubated in D2O as a function of time and temperature to effect isotopic exchange, transferred into slow exchange conditions (pH 2–3, 0 °C), and fragmented with pepsin. The number of peptide amide deuterons present in the proteolytic peptides was deduced from their molecular weights, which were determined following analysis of the digest by HPLC‐FABMS. The present results demonstrate that the exchange rates of amide hydrogens in cytochrome c range from very rapid (k > 140 h−1) to very slow (k < 0.002 h−1). The deuterium content of specific segments of the protein was determined as a function of incubation temperature and used to indicate participation of these segments in conformational changes associated with heating of cytochrome c. For the present HPLC‐FABMS system, approximately 5 nmol of protein were used for each determination. Results of this investigation indicate that the combination of protein fragmentation and HPLC‐FABMS is relatively free of constraints associated with other analytical methods used for this purpose and may be a general method for determining hydrogen exchange rates in specific segments of proteins.
Cascading influence of inorganic nitrogen sources on DOM production, composition, lability and microbial community structure in the open ocean

Nitrogen frequently limits oceanic photosynthesis and the availability of inorganic nitrogen sources in the surface oceans is shifting with global change. We evaluated the potential for abrupt increases in inorganic N sources to induce cascading effects on dissolved organic matter (DOM) and microbial communities in the surface ocean. We collected water from 5 m depth in the central North Pacific and amended duplicate 20 liter polycarbonate carboys with nitrate or ammonium, tracking planktonic carbon fixation, DOM production, DOM composition and microbial community structure responses over 1 week relative to controls. Both nitrogen sources stimulated bulk phytoplankton, bacterial and DOM production and enriched Synechococcus and Flavobacteriaceae; ammonium enriched for oligotrophic Actinobacteria OM1 and Gammaproteobacteria KI89A clades while nitrate enriched Gammaproteobacteria SAR86, SAR92 and OM60 clades. DOM resulting from both N enrichments was more labile and stimulated growth of copiotrophic Gammaproteobacteria (Alteromonadaceae and Oceanospirillaceae) and Alphaproteobacteria (Rhodobacteraceae and Hyphomonadaceae) in weeklong dark incubations relative to controls. Our study illustrates how nitrogen pulses may have direct and cascading effects on DOM composition and microbial community dynamics in the open ocean.
Studies to Investigate the in Vivo Therapeutic Window of the γ-Secretase Inhibitor N2-[(2S)-2-(3,5-Difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-l-alaninamide (LY411,575) in the CRND8 Mouse

Accumulation of amyloid β-peptide (Aβ) is considered a key step in the etiology of Alzheimer's disease. Aβ is produced by sequential cleavage of the amyloid precursor protein by β- and γ-secretase enzymes. Consequently, inhibition of γ-secretase provides a promising therapeutic approach to treat Alzheimer's disease. Preclinically, several γ-secretase inhibitors have been shown to reduce plasma and brain Aβ, although they also produce mechanism-based side effects, including thymus atrophy and intestinal goblet cell hyperplasia. The present studies sought to establish an efficient screen for determining the therapeutic window of γ-secretase inhibitors and to test various means of maximizing this window. Six-day oral administration of the γ-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-l-alaninamide (LY411,575) reduced cortical Aβ40 in young (preplaque) transgenic CRND8 mice (ED50 ≈ 0.6 mg/kg) and produced significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The therapeutic window was similar after oral and subcutaneous administration and in young and aged CRND8 mice. Both the thymus and intestinal side effects were reversible after a 2-week washout period. Three-week treatment with 1 mg/kg LY411,575 reduced cortical Aβ40 by 69% without inducing intestinal effects, although a previously unreported change in coat color was observed. These studies demonstrate that the 3- to 5-fold therapeutic window for LY411,575 can be exploited to obtain reduction in Aβ levels without induction of intestinal side effects, that intermittent treatment could be used to mitigate side effects, and that a 6-day dosing paradigm can be used to rapidly determine the therapeutic window of novel γ-secretase inhibitors.
Psychiatric and neurological symptoms in workers occupationally exposed to organic solvents — results of a differential epidemiological study

It is accepted knowledge today that repeated intoxication with organic solvents damages the central nervous system and causes persistent psycho‐organic symptoms. That long‐term but low‐level occupational exposure — typical of painters and other blue‐collar workers — can also induce such disorders has not generally been recognized. The present epidemiological study was undertaken to evaluate the possible neuropsychiatric effects of such exposure. 80 laquerers exposed to a mixture of industrial solvents (average hygienic effect 0.3) and 37 printers exposed almost only to toluene (average hygienic effect 1.0) were compared with a control group of 80 age‐matched non‐exposed subjects. In psychiatric inteviews, the painters showed more mental symptoms. Fatigue, nervousness and lack of manual dexterity were most important and formed a typical neurasthenic syndrome. A general decrease in conduction velocity and action potential amplitude was also observed for the peripheral nerves. The printers showed a large decrease of the nerve action potential amplitude only for the sural nerve. No EEG abnormalities were found. Nor could any increase in mental symptoms be detected through psychiatric interviews compared to the controls. The results are interpreted as evidence for a CNS affection with consequent neuropsychiatric signs and symptoms after long‐term occupational expo‐sure to mixtures of industrial solvents below the current threshold limit values (TLV) but not after exposure to a single substance like toluene at about the TLV. The differential effects may be explained by synergistic amplification of the toxicity of solvent mixtures.
Cardiovascular Deterioration in STZ-Diabetic Rats: Possible Role of Vascular RAS

The precise mechanisms involved in the etiology of cardiovascular complications in diabetes are undefined. Recent evidence suggests that the renin-angiotensin system plays a predominant role in the genesis of these complications. The temporal evolution of vascular angiotensin-converting enzyme (ACE) activity was evaluated in streptozotocin-diabetic rats 2 and 4 weeks following the induction of diabetes. Vascular ACE activity was correlated with acetylcholine-induced relaxation, systolic blood pressure, and cardiac output index, establishing a possible link between these variables. Age-matched Sprague-Dawley rats were used as controls. ACE activity in aortic homogenates doubled in rats after 2 weeks of diabetes as compared with controls (0.46 ± 0.06 vs. 0.19 ± 0.02 nmol/mg × min, n = 8, p < 0.05). In contrast, no difference was observed between rats 4 weeks following diabetes onset (0.20 ± 0.05 nmol/mg × min) and controls (n = 8, p > 0.05). Impaired endothelial function was also observed in the aorta of diabetic animals. The maximal aortic relaxation with 10 µmol/l acetylcholine was reduced by 40% in diabetic rats 2 weeks after onset and by 41% after 4 weeks when compared to controls (n = 8, p < 0.05). Two weeks following diabetes induction, the cardiac output index decreased by 16% and after 4 weeks by 30% (n = 4, p < 0.05). Systolic blood pressure increased from 116 ± 12 mm Hg before diabetes to 158 ± 4 mm Hg (p < 0.05) after 2 weeks and to 182 ± 5 mm Hg after 4 weeks (p < 0.05). Together, these results suggest that a local renin-angiotensin system plays an important role in the genesis of vascular dysfunction and cardiac deterioration within the first stages of diabetes. A high vascular ACE activity may promote progressive deterioration of the cardiovascular system in streptozotocin-diabetic rats from the earliest stages by increasing peripheral resistance, blood pressure, preload, afterload, and cardiac work.
Effects of a Psychiatric Rotation on Psychiatric Knowledge and Attitudes towards Psychiatry in Rotating Interns

The attitudes of trainees toward Psychiatry affect their career choice and ability to properly identify and manage emotional disorders in their patients. These attitudes are determined by several factors which include preclinical and clinical training among others. We report here a study of the attitude of interns toward psychiatry using the 30 item attitude toward psychiatry (ATP-30) scale. The ATP-30 and a multiple choice questionnaire examination (MCQE) in psychiatry were completed by 96 interns at the beginning and end of their compulsory four week psychiatry rotation. The degree of satisfaction of the trainees was rated in four areas — orientation, teaching/learning experience, overall rating of rotation and relevance of rotation to career choice. There was no significant change in the mean ATP-30 scores (N = 55) during the four week rotation, but the MCQE scores (N = 74) improved significantly (P < 0.0001). A repeated analysis of variance for the four satisfaction variables by change score in MCQE and change score in ATP-30 did not show any significant main effects or significant interactions between these change scores except with relevance of rotation. Reasons for the absence of changes in the ATP-30 scores during this rotation were explored. The implications of the improved knowledge during this rotation are also discussed. We also conclude that attitudinal change and knowledge are two independent factors which should be assessed independently in trainees.
Effects of a pulmonary rehabilitation programme on physiologic and psychosocial outcomes in patients with chronic respiratory disorders.

INTRODUCTION The purpose of this prospective study is to determine the effects of a pulmonary rehabilitation programme (PRP) conducted at our centre for patients with chronic lung disease. MATERIALS AND METHODS Thirty-four patients (27 men and 7 women, mean age 67.7 years) with predominantly moderate-to-severe chronic obstructive pulmonary disease (31 patients), bronchiectasis (2 patients) and interstitial lung disease (1 patient) completed a 6-week outpatient PRP that included education, physical and respiratory care instruction and supervised exercise training. Outcome assessment was performed at baseline, on completion of PRP and 3 months after PRP. Physiologic measures included pulmonary function, incremental exercise and 6-minute walk tests (6MWTs). Disease-specific quality of life was assessed using the Chronic Respiratory Disease Questionnaire (CRDQ). RESULTS There was no significant change in resting spirometry or lung volumes after PRP. Maximal oxygen uptake and work-rate improved significantly after PRP by 132.4 mL kg-1 min-1 and 10.7 W, respectively. 6MWT distance improved significantly by a mean of 67.3 m (P < 0.0001). Maximum Borg dyspnoea scores decreased significantly by 1.2 +/- 0.5 (P < 0.038). All domains of the CRDQ completed by a sub-group of patients improved significantly and the total scores increased by a mean of 21.7 points at the end of the PRP. The improvements gained in maximal exercise capacity immediately following PRP were maintained in 17 patients who returned for repeat assessment 3 months after PRP. CONCLUSION Patients who completed a comprehensive PRP at our centre showed significant increase in functional capacity, reduction of exertional dyspnoea and improvement in health status.
The c‐kit‐encoded tyrosine kinase regulates the proliferation of early pre‐B cells

A monoclonal antibody (mAb; ACK2) recognizing the extracellular domains of the c‐kit‐encoded tyrosine kinase has been employed to demonstrate that c‐kit is involved in B lymphocyte development. The c‐kit‐encoded tyrosine kinase is expressed on the surface of normal DHJH‐rearranged murine pre‐B cell clones which proliferate continuously at that stage in vitro on stromal cells and in the presence of recombinant interleukin 7. These pre‐B cell clones, capable of differentiation to surface immunoglobulin‐positive B cells in vitro and in vivo, are inhibited by the mAb in their proliferation while remaining capable of differentiation to surface immunoglobulin‐positive B cells. Stimulation of mature B cells by mitogens is unimpaired by the mAb. This indicates that c‐kit regulates early antigen‐independent, but not late antigen‐dependent, B cell development.
Recommended and Reported Use of Communication Strategies in Alzheimer Caregiving

Individuals with Alzheimer disease experience cognitive and behavioral impairments that affect their ability to communicate. In an effort to compensate for these declines, a number of communication strategies have been recommended in the literature for Alzheimer disease caregivers. These include recommendations for caregivers to modify their language behavior and/or the context of communication. The purpose of this study was to (1) review the Alzheimer disease caregiving literature and identify communication strategies commonly recommended for family caregivers and (2) determine how often caregivers report using these strategies and how effective they feel each is in facilitating communication. A review of the literature identified 10 recurring communication strategies. A questionnaire was constructed that asked caregivers to report on the use and efficacy of these 10 strategies. Twenty family (spouse) caregivers of persons diagnosed with Alzheimer disease completed the questionnaire. The results show that caregivers perceived using the 10 strategies, although the strategies appearing most frequently in the literature were not necessarily the ones used most often by caregivers. A positive correlation was observed between caregivers' perceived use of strategies and their effectiveness. Use and efficacy of a strategy did not significantly vary as a function of dementia severity or the gender of the caregiver. The findings provide evidence that caregivers are aware of their communication behavior and modify it in ways that they think improve communication with their spouse.
The influence of sex upon the antibody response to an incompatible tumour.

(BALB/c×C57B1) hybrids and strain 129 hosts of both sexes were immunized with heavily irradiated cells of the C3H ascites sarcoma, B.P.8. It was found that both the primary and secondary haemagglutinin responses were higher in females than males of the same strain. After passive immunization, antibody titres declined at equal rates in the two sexes. It is concluded that antibody synthesis is sustained at a higher rate in females than males. Further experiments were performed to investigate the basis of this difference. The effects of oophorectomy and oestrogen replacement treatment indicate that the superior reactivity of females is not due to the presence of ovarian tissues. It is concluded from the effects of orchidectomy that the immunological inferiority of males is due partly to the presence of the testes. However, treatment with testosterone propionate failed to influence the haemagglutinin response to irradiated B.P.8 in two experiments. An acute illness resembling severe `runt disease' was observed in oestrogen treated mice after immunization.
Risk of excessive bleeding associated with marginally low von Willebrand factor and mild platelet dysfunction

Summary. Background: Bleeding symptoms are so commonly reported that it is not known whether they associate causally or coincidentally with mild but measurable primary hemostatic defects. Objectives/patients/methods: In order to evaluate if the mild primary hemostatic defects are truly causative of increased bleeding symptoms, we surveyed a population of healthy teenagers for bleeding symptoms. Using a case–control approach, we then estimated the risk of excessive bleeding associated with low von Willebrand factor (defined as VWF below the 5th percentile of a normal reference population), and with mild platelet dysfunction [PD, defined as concurrent reduced platelet aggregation responses to two agonists (adenosine diphosphate and epinephrine)]. Results: Excessive bleeding was present in 63 out of 809 teenagers (7.8%). Among the 49 cases who were tested for VWF, low values by three measures were more commonly present than in 166 controls, specifically, ristocetin cofactor (RCo) activity [20.4% vs. 5.4%, odds ratio (OR) 4.5], collagen binding (14.3% vs. 4.2%, OR 3.8), and antigen level (20.4% vs. 6.0%, OR 4.0). The low RCo values ranged from 35 to 45 U dL−1 except for a single case with 26 U dL−1. Of the 47 teenagers with excessive bleeding who underwent platelet aggregation studies, reduced responses were more common than in controls (12.8% vs. 4.4%, OR 3.2). Twenty‐nine per cent of cases with excessive bleeding had either low RCo or PD. Conclusion: Almost one in three teenagers who report excessive bleeding is likely to have a measurable hemostatic disturbance manifested either by marginally low VWF (by three measures) or by mild PD.
Leek or Garlic? A Chemical Evaluation of Elephant Garlic Volatiles

“Aglione della Valdichiana” is listed among the Traditional Agronomic and Edible Products of Italy, as it is a typical product of the Chiana Valley (Tuscany, Italy). It is also known as “elephant garlic”, due to the dimension of its cloves, and, other than in the Italian Mediterranean area, its presence is also reported in North Africa and Southwest Asia. The current botanical classification identifies it as a leek variety (Allium ampeloprasum L.), although its appearance, except for its larger dimensions, resembles that of garlic. In the present study, the spontaneous volatile emission of whole and cut cloves of “Aglione della Valdichiana” (elephant garlic), garlic, and leek has been profiled by headspace solid phase micro-extraction. The results have been subjected to statistical analyses (analysis of variance, hierarchical cluster, and principal component analysis) to assess whether the chemical profile confirmed the botanical proximity of elephant garlic and leek, rather than garlic. The phytochemical volatiles evaluation indicated a higher proximity of elephant garlic to garlic, rather than leek, at least for the Chiana Valley specimen analyzed in this study.
Modification of vascular function after handgrip exercise training in 73- to 90-yr-old men.

PURPOSE To examine the influence of a unilateral exercise training protocol on brachial artery reactivity (BAR) in 12 men (aged 81 +/- 5 yr). METHODS Brachial artery diameters and blood flow parameters were assessed, in both arms, using high-resolution ultrasonography, before and after 5 min of forearm occlusion, before and at the end of each week of a 4-wk training program. Training consisted of a unilateral handgrip training protocol (nondominant arm) at 60% of maximal voluntary handgrip strength, performed for 4 wk, 4 d x wk(-1), 20 min per session, and a cadence of one contraction per 4 s. RESULTS After training, handgrip strength increased 6.2% (baseline = 32.4 +/- 7.0 kg vs week 4 = 34.4 +/- 6.7 kg) in the trained arm only but failed to reach statistical significance (P = 0.10). No statistical changes were observed for blood pressure or resting HR. In contrast, BAR increased 45% (Pre = 2.9% vs Post = 4.1%, P = 0.05) in the trained arm only. Improvements in BAR were observed after the second week of training, without significant changes in the main vasodilatory trigger, defined as the relevant shear stimulus after forearm occlusion (P > 0.05). CONCLUSIONS These data indicate that a localized short-term exercise program results in significant improvements in vascular function in the trained arm of elderly men compared with the control arm. Furthermore, the findings indicate a statistically significant increase in BAR at the end of the second week of training, despite a similar trigger for dilation versus before training.
Inflammatory Breast Cancer: Results of Antracycline‐Based Neoadjuvant Chemotherapy

Abstract: Twenty‐three patients with inflammatory breast cancer treated with a combined modality approach including anthracycline‐based induction chemotherapy‐surgery‐chemotherapy‐radiotherapy were reviewed. Twelve patients (52.2%) received FAC (5‐fluorouracil, adriamycin, cyclophosphamide) and 11 patients (47.8%) were treated with FEC (5‐fluorouracil, epirubicin, cyclophosphamide) induction chemotherapy for three cycles every 3 weeks. Surgery was followed by the initial chemotherapy or second‐line chemotherapy for an additional six cycles to complete nine cycles and radiotherapy, respectively. The median overall survival (OS) time was 27 months and the median disease‐free survival (DFS) was 13 months. Furthermore, patients treated with FAC induction chemotherapy have been found to have longer median OS and DFS periods compared to patients with FEC induction chemotherapy in both univariate and multivariate analysis. In conclusion, the superiority of doxorubicin‐containing chemotherapy over epirubicin‐containing chemotherapy should be established in larger randomized studies and more effective chemotherapeutic agents such as taxans are required for better survival rates in inflammatory breast cancer patients.
Modeling of Parasitic Inductive Couplings in a Pi-Shaped Common Mode EMI Filter

This paper analyzes the effects of parasitic inductive couplings among the filter components and printed circuit board traces in a pi-shaped common mode (CM) electromagnetic interference (EMI) filter. The result shows that some parasitic inductive couplings related with CM choke do not affect the CM EMI filter performance. And then, it proposes a high-frequency circuit model for filtration performance evaluation and prediction for pi-shaped CM EMI filter, in which the parasitic inductive coupling between input and output loops of the investigated filter is considered to be the crucial coupling parameter while other parasitic couplings are ignored. The model is simple because only one coupling parameter is involved. A procedure is introduced to extract the inductive coupling between input and output loops in pi-shaped CM EMI filter using Z parameters through virtual prototyping. Simulation and experiment finally validate the model.