Miracle-dz/UniFAR-FTUs huggingface dataset:
How the other half lives, the amino‐terminal domain of the retinoblastoma tumor suppressor protein

The retinoblastoma tumor suppressor gene (RB1) is currently the only known gene whose mutation is necessary and sufficient for the development of a human cancer. Mutation or deregulation of RB1 is observed so frequently in other tumor types that compromising RB1 function may be a prerequisite for malignant transformation. Identifying the molecular mechanisms that provide the basis for RB1‐mediated tumor suppression has become an important goal in the quest to understand and treat cancer. The lion's share of research on these mechanisms has focused on the carboxy‐terminal half of the RB1 encoded protein (pRB). This focus is with good reason since this part of the protein, now called the “large pocket,” is required for most of its known activities identified in vitro and in vivo. Large pocket mediated mechanisms alone, however, cannot account for all observed properties of pRB. The thesis presented here is that the relatively uncharacterized amino‐terminal half of the protein makes important contributions to pRB‐mediated tumor suppression. The goals of this review are to summarize evidence indicating that an amino‐terminal structural domain is important for pRB function and to suggest a general hypothesis as to how this domain can be integrated with current models of pRB function. J. Cell. Physiol. 197: 169–180, 2003© 2003 Wiley‐Liss, Inc.
Decomposing the Labour Productivity Gap between Migrant-Owned and Native-Owned Firms in Sub-Saharan Africa

Abstract Migration studies have been primarily based on the movement of individuals from developing to developed economies, with a focus on the impact of migrants on host country wages. In this study we take a different angle by exploring the labour productivity of migrant-owned firms versus native-owned firms in 20 African economies using firm-level data. We find that labour productivity is 78 per cent higher in migrant-owned firms than native-owned firms. Using the Oaxaca-Blinder decomposition method we find that structural effects account for 80 per cent of the labour productivity gap. Returns to manager education largely explain the productivity advantage of migrant-owned firms over native-owned firms. Interactions with the government, access to finance, informality, and power outages are also considerable contributors to the labour productivity gap.
The impact of treatment-resistant depression on health care utilization and costs.

BACKGROUND Approximately 50% of patients diagnosed with major depressive disorder will experience a recurrent or chronic course of illness for which long-term treatment is recommended. Moreover, at least 20% of patients diagnosed with depression do not respond satisfactorily to several traditional antidepressant medication treatment trials. Very little is known about the health care costs of patients with treatment-resistant depression. METHOD Based on medical claims data (MarketScan Research Database, The MEDSTAT Group, Cambridge, Mass.) from January 1, 1995, to June 30, 2000, a naturalistic, retrospective analysis was conducted to study the characteristics and health care utilization of patients with treatment-resistant depression. All patients having an International Classification of Diseases, Ninth Revision (ICD-9), diagnosis code for unipolar or bipolar depression with specified antidepressant dosing and treatment durations were initially selected. Patients were then classified as "treatment resistant" if either they switched from or augmented initial antidepressant medication with other antidepressants at least twice (outpatient treatment-resistant group) or they switched from or augmented their initial antidepressant medication and also had a claim for either a depression-related hospitalization or suicide attempt (hospitalized treatment-resistant group). Those meeting the initial medication and diagnosis selection criteria but not meeting the treatment-resistance criteria constituted the comparison group. Members of the comparison group had comparatively stable antidepressant medication use patterns, consistent with an acceptable response to treatment. Patients were followed for a minimum of 9 months. Resource utilization was calculated from index date to last available claims data point and then annualized. RESULTS Treatment-resistant patients were more likely to be diagnosed with bipolar disorder or concurrent substance abuse or anxiety disorders than the comparison group (p <.001). Treatment-resistant patients were at least twice as likely to be hospitalized (general medical and depression related) and had at least 12% more outpatient visits (p <.02). Treatment resistance was also associated with use of 1.4 to 3 times more psychotropic medications (including antidepressants) (p <.001). Patients in the hospitalized treatment-resistant group had over 6 times the mean total medical costs of non-treatment-resistant depressed patients ($42,344 vs. $6512) (p <.001) and their total depression-related costs were 19 times greater than those of patients in the comparison group ($28,001 vs. $1455) (p <.001). CONCLUSION Treatment-resistant depression is costly and associated with extensive use of depression-related and general medical services. These findings underscore the need for early identification and effective long-term maintenance treatment for treatment-resistant depression.
Trip Expenditure Comparisons from 1972-73 to 1980-81

Annual travel expenditures by Americans have increased dramatically since 1972-73, according to the 1980-81 Consumer Expenditure Survey . Overall, urban families have increased their vacation and pleasure trip expenses by 145 percent, from $272 to $667 . The largest increase was for transportation-186 percent, followed by: entertainment and other expenses-144 percent, lodging-132 percent, and food and beverages-99 percent. During this same period, prices for the transportation component of trips increased about 165 percent, entertainment services-57 percent, and lodging out of town-120 percent, while food prices about doubled . ' As a percentage of total trip expenses, families spent the most on transportation, followed by food and beverages, lodging, and all other expenses . Within respective expenditure categories, gas and oil increased the most for all consumer units-205 percent. During this same period, the Consumer Price Index for gasoline and motor oil increased 246 percent. A comparison of income and age groups shows that the largest percentage increase for trips occur -red in the lowest 20 percent quintile income group (296 percent) and in the under 25 age group (216 percent) . (Ages given refer to the reference person .) However, the level of expenditures for these groups was only 40 percent and 60 percent of the all consumer unit average. Families in the 45 to 54 age group and families in the highest 20 percent quintile group continued to have higher-than-average dollar expenditures on vacation and pleasure trips. Overall, trip expenditures increased by income class . Similarly, trip expenses rose by age group until the 65 and over category where expenditures declined . The over 65 age group spent less on trips than most age groups in both 1972-73 and 1980-81 . Whereas trip expenditures tripled for most other age groups, expenditures for families 65 and over only doubled. z
Shipping Policy to Fight the Resource Curse

Transnational trade rules endow authoritarians and armed groups with unaccountable power in states rich with natural resources. This structural flaw in international trade generates the â€˜resource curseâ€™ phenomena that have driven many of the world's most serious crises since the 1970s. Attempts to curtail this unaccountable power from outside resourceâ€ rich states have not been successful, and crises caused by this structural flaw continue to plague the global community. The shipping sector provides a promising location for reforms to fight the resource curse, as it is a sector where extensive, unified and enforceable regulations have long been established.
Followership and Leadership in Medium-Sized Enterprises in the Republic of Bulgaria

Good leaders need followers. Without great followers, leaders would become schizophrenics sitting in their offices talking to themselves. Can a person be defined as good leader if he does not have any people to believe in him, to follow his example, to trust him? Followership is a process when the person has the capacity and willingness to follow the leader when having some target. In other words, being a good follower means having the skills, the abilities, and the desire to follow the leader in achieving the goals. The chapter aims to define what is followership, how it is related to leadership, especially in business organizations such as medium-sized enterprises. Thus, followership can be perceived as a mutual process in which the leaders and followers interact, help each other to reach the aims on individual and organizational level. The importance of followership to the leader will be analyzed followed by author's recommendations for the future and a conclusion.
Brain sites of action of endogenous interleukin‐1 in the febrile response to localized inflammation in the rat

1 Interleukin (IL)‐1 is a potent endogenous pyrogen which causes fever when injected into a number of brain sites. However, the brain sites at which endogenous IL‐1 acts to influence body temperature remain equivocal. The aim of this study was to determine the effect of local administration of the interleukin‐1 receptor antagonist (IL‐1ra) into specific sites in the hypothalamus, and other brain regions known to contain receptors for IL‐1, on the febrile response of rats to peripheral injection of lipopolysaccharide (LPS) into a subcutaneous air pouch (intrapouch, i.p.o.) that does not lead to LPS appearance in the circulation. 2 Injection of LPS (100 μg kg−1, i.p.o.) induced a rise in body temperature which commenced 1·5 h after injection and was maximal at 3 h (38·9 ± 0·2 °C, compared with 37·0 ± 0·1 °C at 0 h, n= 6, P < 0·001). Intracerebroventricular (i.c.v.) IL‐1ra (500 μg in 5 μl) significantly attenuated LPS fever (IL‐1ra, 37·7 ± 0·2 °C; saline, 38·9 ± 0·2 °C; n= 6, P < 0·001). Unilateral microinjection of IL‐1ra (50 μg in 0·5 μl at 0 + 1 h) into the anterior hypothalamus (AH), paraventricular hypothalamic nucleus (PVH), peri‐subfornical organ, subfornical organ (SFO) or hippocampus (dentate gyrus and CA3 region) also significantly reduced the fever induced by LPS. 3 The same dose of IL‐1ra had no effect on fever when administered into the ventromedial hypothalamus (VMH), organum vasculosum lamina terminalis (OVLT), CA1 field of the hippocampus, striatum or cortex. 4 These data indicate that the action of endogenous IL‐1 in the brain during fever is site specific, acting at the AH, PVH, SFO and hippocampus, but not the VMH, OVLT and striatum or cortex.
In vitro evaluation of the effects of gefitinib on the cytotoxic activity of selected anticancer agents in a panel of human endometrial cancer cell lines

Purpose. This study was conducted to determine the in vitro optimal combination of selected anticancer agents with gefitinib and evaluate its effect on the expression of correlative biological targets in the cell-signaling pathway. In addition, the effect of gefitinib on the expression of ATP-binding cassette (ABC) transport proteins was evaluated. Methods. Growth inhibition assays were conducted in six human endometrial cancer cell lines to evaluate the activity of selected anticancer agents with gefitinib compared to each alone. Enzyme linked immunosorbant assay (ELISA) assessed the presence of pEGFR in treated and untreated cells. Evaluation of the suppression of correlative biological targets in the cell-signaling pathway was completed by immunoblotting. RT-PCR was used to characterize the expression of MRP and ABC transport proteins. Results. This in vitro study gefitinib did not observe cytotoxic activity as a single agent. However, the activity of gefitinib as EGFR inhibitor was confirmed. The combination of gefitinib with paclitaxel and docetaxel exhibited improved in vitro cytotoxic activity compared to each antineoplastic agent alone. Suppression of pAKT and p27 in the human endometrial cancer cells treated with selected combinations of chemotherapeutic drugs and gefitinib was observed. Conclusion. These data suggest that EGFRinhibitors, such as gefitinib, have the potential to modulate common mechanisms of drug resistance and may have a role in optimizing antineoplastic regimens for the treatment of recurrent endometrial cancer. This may represent a promising option for this class of agents in the treatment of endometrial cancer. J Oncol Pharm Practice (2009) 15: 35—44.
Pandora : une plate-forme efficace pour la construction d'applications autonomes

L'informatique autonome a recemment ete proposee comme une reponse a la difficulte de gerer au quotidien des applications dont la complexite ne cesse d'augmenter. Les applications autonomes devront etre particulierement flexibles et pouvoir se surveiller en permanence. Cette etude presente une plate-forme, Pandora, qui facilite la construction d'applications qui satisfont ce double objectif. Pandora s'appuie sur un mode de programmation original des applications - fonde sur la composition de couches et le passage de messages - pour aboutir a un modele et une architecture minimalistes qui lui permettent de controler les surcouts imposes par la complete reflexivite de la plate-forme. Un prototype fonctionnel de la plate-forme a par ailleurs ete developpe en C++. Une etude detaillee des performances, ainsi que des exemples d'utilisation, completent cette presentation. ––––– Autonomic computing has been proposed recently as a way to address the difficult management of applications whose complexity is constantly increasing. Autonomous applications will have to be especially flexible and be able to monitor themselves permanently. This work presents a framework, Pandora, which eases the construction of applications that satisfy this double goal. Pandora relies on an original application programming pattern - based on stackable layers and message passing - to obtain minimalist model and architecture that allows to control the overhead imposed by the full reflexivity of the framework. Besides, a prototype of the framework has been implemented in C++. A detailed performance study, together with examples of use, complement this presentation
Comparing Rule-based and SMT-based Spelling Normalisation for English Historical Texts

To be able to use existing natural language processing tools for analysing historical text, an important preprocessing step is spelling normalisation, converting the original spelling to present-day spelling, before applying tools such as taggers and parsers. In this paper, we compare a probablistic, language-independent approach to spelling normalisation based on statistical machine translation (SMT) techniques, to a rule-based system combining dictionary lookup with rules and non-probabilistic weights. The rule-based system reaches the best accuracy, up to 94% precision at 74% recall, while the SMT system improves each tested period.
Increased uterine artery vascular impedance is related to adverse outcome of pregnancy but is present in only one‐third of late third‐trimester pre‐eclamptic women

Signs of increased uterine artery vascular impedance in mid‐gestation are strongly related to pre‐eclampsia later in pregnancy. Whether this is true for the late third trimester is, however, unclear. The aim of the present study was to analyze the frequency of increased uterine artery vascular impedance in the third trimester, and its relationship to abnormal umbilical artery Doppler and adverse outcome of pregnancy.
Novel Varactor-Tuned Coupling Mechanism and Its Applications to High-Order Bandwidth-Agile Bandpass Filters

In this paper, a novel tunable coupling mechanism with bandwidth-tunable capability is presented. Metallic via has been utilized to construct the coupling structure, namely via-coupling. Studies show that the via-coupling mechanism provides more flexibility and owns better tolerance to fabrication errors than the traditional gap-coupling. By employing varactor in parallel with the metallic via, the coupling coefficient between each resonator pairs can be effectively tuned. It is worth noting that only one varactor is required for each resonator pair. The lumped-circuit model of the tunable coupling mechanism is investigated and extracted by classical theory derivation and simple programming. For verification, a fourth-order quasi-elliptic bandpass filter (BPF) and a bandwidth-tunable one are designed, fabricated, and measured. For the bandwidth-tunable BPF, the factional bandwidth varies from 2.52% to 5.04%, meaning a double tuning range. The in-band insertion loss varies from 2.8 to 4.8 dB, and the return loss is better than 17 dB. If needed, BPFs with <inline-formula> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula>th-order (<inline-formula> <tex-math notation="LaTeX">$N > 4$ </tex-math></inline-formula>) could be designed based on the proposed tunable coupling mechanism and only (<inline-formula> <tex-math notation="LaTeX">$N + 1$ </tex-math></inline-formula>) varactors are required.
Hypoxia Inducible Factor 1 Mediates Hypoxia-Induced TRPC Expression and Elevated Intracellular Ca2+ in Pulmonary Arterial Smooth Muscle Cells

Chronic hypoxia (CH) causes pulmonary vasoconstriction because of increased pulmonary arterial smooth muscle cell (PASMC) contraction and proliferation. We previously demonstrated that intracellular Ca2+ concentration ([Ca2+]i) was elevated in PASMCs from chronically hypoxic rats because of Ca2+ influx through pathways other than L-type Ca2+ channels and that development of hypoxic pulmonary hypertension required full expression of the transcription factor hypoxia inducible factor 1 (HIF-1). In this study, we examined the effect of CH on the activity and expression of store-operated Ca2+ channels (SOCCs) and the regulation of these channels by HIF-1. Capacitative Ca2+ entry (CCE) was enhanced in PASMCs from intrapulmonary arteries of rats exposed to CH (10% O2; 21 days), and exposure to Ca2+-free extracellular solution or SOCC antagonists (SKF96365 or NiCl2) decreased resting [Ca2+]i in these cells. Expression of TRPC1 and TRPC6, but not TRPC4, mRNA and protein was increased in PASMCs from rats and wild-type mice exposed to CH, in PASMCs from normoxic animals cultured under hypoxic conditions (4% O2; 60 hours), and in PASMCs in which HIF-1 was overexpressed under nonhypoxic conditions. Hypoxia-induced increases in basal [Ca2+]i and TRPC expression were absent in mice partially deficient for HIF-1. These results suggest that increased TRPC expression, leading to enhanced CCE through SOCCs, may contribute to hypoxic pulmonary hypertension by facilitating Ca2+ influx and increasing basal [Ca2+]i in PASMCs and that this response is mediated by HIF-1.
A Rapid, High-Throughput Viability Assay for Blastocystis spp. Reveals Metronidazole Resistance and Extensive Subtype-Dependent Variations in Drug Susceptibilities

ABSTRACT Blastocystis is an emerging protistan parasite of controversial pathogenesis. Although metronidazole (Mz) is standard therapy for Blastocystis infections, there have been accumulating reports of treatment failure, suggesting the existence of drug-resistant isolates. Furthermore, very little is known about Blastocystis susceptibility to standard antimicrobials. In the present study, we established resazurin and XTT viability microassays for Blastocystis spp. belonging to subtypes 4 and 7, both of which have been suggested to represent pathogenic zoonotic subtypes. The optimized resazurin assay was used to screen a total of 19 compounds against both subtypes. Interestingly, subtype 7 parasites were resistant to Mz, a 1-position-substituted 5-nitroimidazole (5-NI), while subtype 4 parasites were sensitive. Some cross-resistance was observed to tinidazole, another 1-position 5-NI. Conversely, subtype 4 parasites were resistant to emetine, while subtype 7 parasites were sensitive. Position 2 5-NIs were effective against both subtypes, as were ornidazole, nitazoxanide, furazolidone, mefloquine, quinicrine, quinine, cotrimoxazole (trimethoprim-sulfamethoxazole), and iodoacetamide. Both subtypes were resistant to chloroquine, doxycycline, paromomycin, ampicillin, and pyrimethamine. This is the first study to report extensive variations in drug sensitivities among two clinically important subtypes. Our study highlights the need to reevaluate established treatment regimens for Blastocystis infections and offers clear new treatment options for Mz treatment failures.
Left Ventricular Hypertrophy: The Relationship between the Electrocardiogram and Cardiovascular Magnetic Resonance Imaging

Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow–Lyon, Romhilt–Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping, extracellular volume fraction (ECV) mapping, fat/water‐weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH.