Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of epidermal Langerhans cell migration by lactoferrin

Lactoferrin (LF) is a member of the transferrin family of iron‐binding glycoproteins to which several anti‐inflammatory functions have been ascribed. LF has been shown to down‐regulate expression of the pro‐inflammatory cytokine tumour necrosis factor‐α (TNF‐α), although the possibility has been raised that the activity of LF in this regard was indirect and secondary to its ability to bind to and inactivate the bacterial lipopolysaccharide (LPS) used to induce cytokine production. However, the identification of putative membrane receptors for LF raises the possibility that the interaction of LF with its receptor may be one important route through which this protein exerts anti‐inflammatory activity. In the present investigations the biological properties of LF have been examined in a model of cutaneous immune function where the allergen‐induced migration of epidermal Langerhans cells (LC) from the skin and their subsequent accumulation as dendritic cells (DC) in skin‐draining lymph nodes are known to be dependent upon the de novo synthesis of TNF‐α, but independent of exogenous LPS. Consistent with the protein having direct anti‐inflammatory properties, it was found that the intradermal injection of recombinant murine LF (either iron‐saturated or iron‐depleted LF) inhibited significantly allergen (oxazolone) ‐induced LC migration and DC accumulation. That these inhibitory effects were secondary to the inhibition of local TNF‐α synthesis was suggested by the findings that first, LF was unable to inhibit LC migration induced by intradermal injection of TNF‐α itself, and second, that migration stimulated by local administration of another epidermal cytokine, interleukin 1β, which is also dependent upon TNF‐α production, was impaired significantly by prior treatment with LF. Finally, immunohistochemical analyses demonstrated the presence of LF in skin, associated primarily with keratinocytes. Collectively these data support the possession by LF of direct immunomodulatory and/or anti‐inflammatory activity, probably associated in this case with inhibition of cytokine production. Furthermore, the results suggest that as a constituent of normal skin, LF may play a role in homeostatic regulation of cutaneous immune function.
Vaccine preventable meningitis in Malaysia: epidemiology and management

Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9–25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.
Specific heat flow rate: an on-line monitor and potential control variable of specific metabolic rate in animal cell culture that combines microcalorimetry with dielectric spectroscopy.

One of the requirements for enhanced productivity by the animal culture systems used in biotechnology is the direct assessment of the metabolic rate by on-line biosensors. Based on the fact that cell growth is associated with an enthalpy change, it is shown that the specific heat flow rate is stoichiometrically related to the net specific rates of substrates, products, and indeed to specific growth rate, and therefore a direct reflection of metabolic rate. Heat flow rate measured by conduction calorimetry has a technical advantage over estimates for many material flows which require assays at a minimum of two discrete times to give the rate. In order to make heat flow rate specific to the amount of the living cellular system, it would be advantageous to divide it by viable biomass. This requirement has been fulfilled by combining a continuous flow microcalorimeter ex situ with a dielectric spectroscope in situ, the latter measuring the viable cell mass volume fraction. The quality of the resulting biosensor for specific heat flow rate was illustrated using batch cultures of Chinese hamster ovary cells (CHO 320) producing recombinant human interferon-gamma (IFN-gamma) during growth in a stirred tank bioreactor under fully aerobic conditions. The measuring scatter of the probe was decreased significantly by applying the moving average technique to the two participant signals. It was demonstrated that the total metabolic rate of the cells, as indicated by the specific heat flow rate sensor, decreased with increasing time in batch culture, coincident with the decline in the two major substrates, glucose and glutamine, and the accumulation of the by-products, ammonia and lactate. Furthermore, the specific heat flow rate was an earlier indicator of substrate depletion than the flow rate alone. The calorimetric-respirometric ratio showed the intensive participation of anaerobic processes during growth and the related IFN-gamma production. Specific heat flow rate was monotonically related to specific cell growth rate and associated with specific IFN-gamma production. Specific heat flow rate is potentially a valid control variable for the growth of genetically engineered cell lines producing target proteins.
Fractionated Irradiation Can Induce Functionally Relevant Multidrug Resistance Gene and Protein Expression in Human Tumor Cell Lines

Abstract Bottke, D. , Koychev, D. , Busse, A. , Heufelder, K. , Wiegel, T. , Thiel, E. , Hinkelbein, W. and Keilholz, U. Fractionated Irradiation Can Induce Functionally Relevant Multidrug Resistance Gene and Protein Expression in Human Tumor Cell Lines. Radiat. Res. 170, 41–48 (2008). The molecular basis of radiotherapy-related multidrug resistance (MDR) is still unclear. Here we report on a study investigating the effect of fractionated irradiation on expression of the MDR-associated proteins P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and lung resistance-related protein (LRP), the respective mRNAs, and the functional consequences. Cells of six colon and five breast cancer cell lines were irradiated with a total dose of 27 Gy, five fractions of 1.8 Gy per week. The mRNA expression was measured by quantitative RT-PCR, protein levels and drug sensitivity to cisplatin, doxorubicin and bendamustine were assessed by flow cytometry. Breast cancer cell lines showed enhancement of the mRNAs encoding for P-gp, MRP1 and LRP in comparison to nonirradiated cells. No up-regulation of the three mRNA species was observed in the colon cancer cell lines. After irradiation, three breast cancer cell lines showed an up-regulation of LRP, one line an up-regulation of MRP1, and four lines a small up-regulation of P-gp. In the colon cancer cell lines, radiation induced significant enhancement of all three proteins. In comparison to controls, the irradiated cells lines showed a significant resistance to cisplatin, doxorubicin and bendamustine. This study confirms the prior reports of enhancement of P-gp and MRP1 after irradiation, which is accompanied by a multidrug resistance phenomenon, but in addition proposes a novel mechanism in the appearance of MDR after radiation-induced enhancement of LRP.
Course and Outcome after the First Manic Episode in Patients with Bipolar Disorder: Prospective 12-Month Data from the Systematic Treatment Optimization Program for Early Mania Project

Objective: To describe clinical characteristics, course, and outcome during a 1-year period after the first manic episode in patients with bipolar disorder (BD). Methods: This paper describes the project design, demographics, clinical outcomes, and predictors at 6 months to 1 year of follow-up of the first 53 recruited subjects with first-episode mania from the Systematic Treatment Optimization Program for Early Mania. Results: Survival analysis for recurrence of mood episodes showed that 46.7% of patients survived without a mood episode during 1-year of follow-up, and the mean time-to-mood event was 7.9 months. Earlier age of onset was the only variable that significantly predicted recurrence of mood episodes. When examined separately, the survival rates were 76% for a manic episode and 58.7% for a depressive episode. Conclusion: These results suggest that recurrences are common after the first manic episode with more than one-half of the patients experiencing a mood event within 12 months. Aggressive treatment strategies aimed at preventing depressive episodes are needed in the management of early course BD.
The liver X receptor agonist TO901317 protects mice against cisplatin-induced kidney injury

Liver X receptors are in the nuclear receptor superfamily and are contained in the regulation of lipid and cholesterol metabolism. Besides, liver X receptors are considered crucial regulators of the inflammatory response and innate immunity. The current study evaluates the in vivo effects that the synthetic liver X receptor agonist TO901317 protects against cisplatin-induced kidney injury in mice. Mice received cisplatin administration through a single intraperitoneal injection (20 mg/kg in saline). And then the mice were treated with the TO901317 by daily gavage (10 mg/kg/day) 12 h postcisplatin administration, and cisplatin nephrotoxicity was evaluated. At 72 h after cisplatin treatment, elevated plasma urea and creatinine levels (P < 0.05) were evidenced which indicates the renal dysfunction of the vehicle-treated mice, consistent with tubular necrosis, protein cast, dilation of renal tubules, and desquamation of epithelial cells in renal tubules. In contrast, the severity of renal dysfunction and histological damage was reduced in TO901317 treated mice (P < 0.05). In accordance, circulating tumor necrosis factor alpha levels, renal tumor necrosis factor alpha, p47phox, gp91phox, and protein expression levels and COX-2 mRNA, renal monocyte chemoattractant protein 1, VACAM-1 mRNA and intercellular adhesion molecule-1 contents, and renal prostaglandin E2 amounts, were higher in samples from cisplatin-treated mice in comparison with controls (P < 0.05) but attenuated in the TO901317 treatment group (P < 0.05). Taken together, treatment with the liver X receptor agonist TO901317 ameliorated the inflammatory response and oxidative stress in cisplatin-induced kidney injury in mice.
‘The Afrikaners’: Disposal of history or a new beginning?

Hermann Giliomee is without doubt one of the most outstanding Afrikaansspeaking historians. If it were necessary to prove this, he has done so with his magnum opus, The Afrikaners: Biography of a People (Giliomee, 2003). This voluminous work is exhaustive in its empirical basis, excellently written and full of surprises, new ideas and perspectives. Certainly for a long time to come, it will remain the standard work on the history of the Afrikaners. This book of more than 650 pages is divided into 17 chapters and contains a complete history of the Afrikaners from 1652 up to the present. However, Giliomee does not always proceed chronologically within the chapters, and rather divides them into smaller subchapters grouped around certain topics. This was a prudent decision, since it enhances the clarity of his narrative. Nevertheless, if the order of Chapters 10 and 11 had been reversed, both would have better fitted into chronology as well as given more stringency to his argument. Less appreciably, I found the footnotes provided, in many cases, only indirect evidence for his quotations from primary sources; sometimes it was even difficult to identify the persons he quoted. But these are only minor criticisms, which should not detract from the fact that this book is a masterly synthesis, albeit a not unproblematic piece of historiography. The book sets a clear accent on twentieth century history, because only 280 pages are devoted to the history up to and including the South African War. This emphasis on contemporary history can be read as a first indication that Giliomee has a political purpose. A closer look reveals that the argumentation is thoroughly influenced by apartheid and its demise. It can therefore be interpreted as an alternative to a new dominant historiography, especially since the history of apartheid has so far been written largely from the perspective of resistance and opposition to it. It is indeed a welcome and refreshing addition, because Giliomee does not pay reverence to notions of political correctness as some other authors do. That is why I enjoyed reading this book, although it is written from a clearly identifiable, conservative perspective, which I do not share. I learned with relish that it lacks the eagerness, with which some writers lately tried to correct Politikon, (May 2005), 32(1), 139–147
A universal VAD based on jointly trained deep neural networks

In this paper, we propose a joint training approach to voice activity detection (VAD) to address the issue of performance degradation due to unseen noise conditions. Two key techniques are integrated into this deep neural network (DNN) based VAD framework. First, a regression DNN is trained to map the noisy to clean speech features similar to DNN-based speech enhancement. Second, the VAD part to discriminate speech against noise backgrounds is also a DNN trained with a large amount of diversiﬁed noisy data synthesized by a wide range of additive noise types. By stacking the classiﬁcation DNN on top of the enhancement DNN, this integrated DNN can be jointly trained to perform VAD. The feature mapping DNN serves as a noise normalization module aiming at explicitly generating the “clean” features which are easier to be correctly recognized by the following classiﬁcation DNN. Our experiment results demonstrate the proposed noise-universal DNN-based VAD algorithm achieves a good generalization capacity to unseen noises, and the jointly trained DNNs consistently and signiﬁcantly outperform the conventional classiﬁcation-based DNN for all the noise types and signal-to-noise levels tested.
Bioactive terpenoids from the Red Sea soft coral Sinularia polydactyla

Chemical investigation of an ethyl acetate soluble fraction of Sinularia polydactyla (Ehrenberg) led to the isolation of three known terpenoides, two of them sterols, 24-methylcholestane-3β,5α,6β,25-tetrol 25-monoacetate (1), 24-methylcholestane-5-en-3β,25-diol (2), in addition to a cembranoid diterpene, durumolide C (3), for the first time. The cytotoxicity and antimicrobial activities of the ethyl acetate extract and the isolated compounds 1–3 were evaluated in vitro. Durumolide C (3) showed selective cytotoxicity against HepG2 (IC50 1.0 μg/mL), whereas 24-methylcholestane-3β,5α,6β,25-tetrol 25-monoacetate (1) showed IC50 of 6.1 and 8.2 μg/mL against Hep2 and HCT human cancer cell lines, respectively.
Electromagnetic Susceptibility Measurements Using a Mode-Stirred Chamber

Within the electromagnetic compatibility community it is recognized that there is a need for better methods to measure the radiat1 2 3 ed susceptibility of electronic systems. ' ' Free-space measurement facilities are economi­ cally unattractive, and the usual recourse is to conduct susceptibility tests within shielded rooms. Shielded room data are not, however, solely indicative of the test specimen characteristics; such data are influenced by room characteristics such as size, shape, and loss as well as location of the specimen and associated test equip­ ment within the room. It is easy, however, to convert any standard shielded room into a "mode-stirred" chamber wherein radiated susceptibility tests can be performed with results that are accurate, repeatable, and independent of test set-up. The problem of relating free-space and mode-stirred environ­ ments is approached in two ways, with the end result being a calibration graph that relates chamber input power to equivalent plane wave power density inside the chamber. The accuracy of mode-stirred chamber data is demonstrated by comparing susceptibility profiles from both free-space and modestirred test environments.
Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens.

OBJECTIVES Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. METHODS Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. RESULTS Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. CONCLUSIONS These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these associations.
Nisei: The Quiet Americans

Hailed at the time of its publication in 1969, Bill Hosokawa's 'Nisei' remains an inspiring account of the original Japanese immigrants and their role in the development of the West. Hosokawa recounts the ordeals faced by the immigrant generation and their American-born offspring, the Nisei; the ill-advised government decisions that led to their uprooting during World War II; how they withstood harsh camp life; and their courageous efforts to prove their loyalty to the United States.
Effect of Reperfusion Late in the Phase of Reversible Ischemic Injury: Changes in Cell Volume, Electrolytes, Metabolites, and infrastructure

The acute effects of reperfusion on myocardium reversibly damaged by 15 minutes of severe ischemia in vivo, were studied. Changes in the adenine nudeotide pool, cell volume regulation, myocardial calcium, and ultrastructure were studied at the end of 15 minutes of ischemia and after 0.5, 3.0, and 20 minutes of reflow. Before reperfusion, adenosine triphosphate and the adenylate pool decreased by 63% and 44% of control, respectively, and the adenylate charge was reduced to 0.65. After 3 minutes of reperfusion, the adenylate charge was restored to control by the rephosphorylation of adenosine mono- and diphosphate, but adenosine triphosphate was still reduced by 45%. Mild tissue edema was detected after 0.5 minute of reflow and persisted throughout 20 minutes of reperfusion. The increased tissue water was accompanied by a slight increase in sodium and a marked increase in tissue potassium. Although massive calcium accumulation develops when irreversibly injured tissue is reperfused, no calcium overload was detected during early reperfusion of reversibly injured myocytes. Reperfusion for 3 minutes exaggerated the mitochondrial swelling induced by 15 minutes of ischemia but after 20 minutes of reperfusion, myocardial ultrastructure was essentially normal except for rare swollen, or disrupted, mitochondria. Thus, the cellular abnormalities associated with brief periods of ischemia persist for variable periods of time after reperfusion of reversibly injured myocytes. First: although adenine nudeotide repletion occurs very slowly, the adenylate charge was restored after 3 minutes, indicating rapid resumption of mitochondrial adenosine triphosphate production. Second: caldum overload was not detected, but myocardial edema and increased potassium persisted throughout the 20 minutes of reperfusion. Third: the ultrastructural consequences of ischemia were nearly reversed after 20 minutes of reperfusion.
Abetimus sodium: a new therapy for delaying the time to, and reducing the incidence of, renal flare and/or major systemic lupus erythematosus flares in patients with systemic lupus erythematosus who have a history of renal disease

The safety and efficacy of abetimus sodium (abetimus) has been evaluated in 13 controlled and uncontrolled clinical trials involving > 800 patients or subjects. The two pivotal trials enrolled a total of 547 patients with systemic lupus erythematosus (SLE) who had a history of lupus nephritis. Evidence of clinical effectiveness of abetimus comes from analyses of data from patients with SLE and high-affinity antibodies to the DNA epitope of abetimus at baseline; a retrospective subgroup in the pivotal Phase II/III LJP-394-90-05 trial (90-05 trial) and the intent-to-treat population in the Phase III LJP-394-90-09 trial (90-09 trial). These studies enrolled SLE patients who had experienced prior renal manifestations of their disease and had elevated anti-dsDNA antibodies at baseline by Farr assay. Both were long-term studies, with a mean duration of treatment participation of 371 days in 90-05 and 310 days in 90-09 for the population of patients with high-affinity antibodies at baseline. The 90-05 and 90-09 studies, as well as all other clinical studies of abetimus, consistently showed that treatment with abetimus resulted in durable and persistent reductions in anti-dsDNA antibodies in SLE patients. Treatment with abetimus was associated with statistically significant decreases in anti-dsDNA antibody levels from baseline compared with placebo in both the 90-09 and 90-05 trials. Positive trends were noted for the incidence of renal flares and major SLE flares in patients treated with abetimus. Abetimus appeared to be well tolerated for treatment periods of ≤ 22 months.