Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of mTOR and EGFR Kinase Inhibitors Blocks mTORC1 and mTORC2 Kinase Activity and Suppresses the Progression of Colorectal Carcinoma

Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. The second generation of mTOR inhibitors such as PP242 targets mTOR kinase; thus, they are capable of inhibiting both mTORC1 and mTORC2. To examine the therapeutic potential of the mTOR kinase inhibitors, we treated a panel of colorectal carcinoma cell lines with PP242. Western blotting showed that the PP242 inhibition of mTORC2-mediated AKT phosphorylation at Ser 473 (AKTS473) was transient only in the first few hours of the PP242 treatment. Receptor tyrosine kinase arrays further revealed that PP242 treatment increased the phosphorylated epidermal growth factor receptor (EGFR) at Tyr 1068 (EGFRT1068). The parallel increase of AKTS473 and EGFRT1068 in the cells following PP242 treatment raised the possibility that EGFR phosphorylation might contribute to the PP242 incomplete inhibition of mTORC2. To test this notion, we showed that the combination of PP242 with erlotinib, an EGFR small molecule inhibitor, blocked both mTORC1 and mTORC2 kinase activity. In addition, we showed that the combination treatment inhibited colony formation, blocked cell growth and induced apoptotic cell death. A systemic administration of PP242 and erlotinib resulted in the progression suppression of colorectal carcinoma xenografts in mice. This study suggests that the combination of mTOR kinase and EGFR inhibitors may provide an effective treatment of colorectal carcinoma.
Interpretation of electrocardiograms by doctors

After marking examination papers of medical students, one of us (HM) found that only one in 50 students correctly identified the PR and QT intervals of the electrocardiogram. As a cardiothoracic surgeon was also unable correctly to identify these intervals we investigated whether such knowledge was lacking in doctors in general. An illustration of a standard electrocardiogram (8 cm × 3 cm) was presented on a single sheet of A4 paper. One hundred and fifty eight doctors of diverse specialty and seniority (table) were asked to mark the PR and QT intervals with arrows. These intervals are defined in a standard way internationally and are discussed in various text books. *RF 1-5* If a candidate was able successfully to mark the PR interval and to state what time interval the smallest square on an electrocardiogram represents when recording at standard speed (25 mm/s), he or …
The effects of treatment on delayed cutaneous hypersensitivity responses (DNCB, croton oil, and recall antigen) in patients with genitourinary cancer

Delayed cutaneous hypersensitivity and inflammatory responses were evaluated in patients with various types and stages of genitourinary cancer. The study was designed to evaluate the influence of tumor type, tumor stage, surgery, radiation therapy, and the course of the malignancy upon the skin test responses. Renal, prostate and bladder cancer patients had significant depressions in their response to recall antigens, DNCB, and croton oil. Impairment of primary delayed hypersensitivity (DNCB response) correlated with tumor stage in bladder but not renal and prostate cancer. Recall antigen response failed to correlate well with stage of disease and was of less value in assessing host immunocompetance. Differences in the effect of cancer on the immune system were found between bladder cancer and renal and prostate cancer patients. These may be explained by variation in cell origin, differences in host response or other characteristics of each type of cancer. The frequency of impaired inflammatory reactions (to croton oil) indicate that defects exist in both the inflammatory and immune mechanisms. The skin test responsiveness following radiation therapy was markedly depressed in a group of bladder cancer patients. However, skin test response in the entire cancer population (renal, prostate and bladder) was not affected by radiation. No significant differences in response could be attributed to the dose of radiation. Changes in response noted after surgery and anesthesia varied depending upon the time interval that elapsed between the skin test and surgery. Patients tested within 10 days of surgery demonstrated depression of skin test responsiveness, whereas those tested 4 to 12 months later demonstrated a significant increase in DNCB responsiveness, presumably due to tumor removal. Tumor removal permitted return of primary and secondary delayed hypersensitivity and inflammatory reactions over a period of many months. Prognostic value was greater for DNCB tests. Survival was poorer in those patients initially unresponsive to DNCB.
Variation in Body Composition in Professional Soccer Players: Interseasonal and Intraseasonal Changes and the Effects of Exposure Time and Player Position

Carling, C and Orhant, E. Variation in body composition in professional soccer players: interseasonal and intraseasonal changes and the effects of exposure time and player position. J Strength Cond Res 24(5): 1332-1339, 2010-The aim of this study was to examine variations in measures of body composition in elite soccer players. Skinfolds and measures of body mass (BM) recorded on a monthly basis across an entire competitive season in a group of senior professional players (n = 26) were used to estimate percentage body fat (%BF) and provide fat-free body mass (FFBM) values. Mean values in players were compared between 6 specific positional roles (goalkeepers, central and lateral defenders/midfielders and center-forwards). In-season variations in measures were studied by comparing values at 5 separate points across the season. The effects of positional group (goalkeepers, defenders, midfielders, and forwards) and exposure time to play (participation time in training and matches) in relation to in-season variations were also examined. To investigate interseasonal changes, repeated measures were taken in players (n = 9) over 3 consecutive seasons. In relation to positional role, a difference in average %BF and BM values was observed (p < 0.001), with substantial differences observed in goalkeepers, lateral midfielders, and forwards. Across all players, there were significant in-season variations in %BF (between start- and mid-season and mid- and end-season, p < 0.001) and FFBM (between start- and mid-season and start- and end-season, p < 0.001), whereas BM remained unchanged. Further analysis of these fluctuations in %BF and FFBM at different points of the season showed that variations differed across the positional groups (p < 0.01), especially in defenders and midfielders. In contrast, no association was observed between measures and exposure time and no differences were reported across seasons. Practitioners should consider individual positional role when interpreting mean body composition data. They should also take into account positional groups when in-season variations in body composition are identified.
The “Cavitary” Type of Angiogenesis by Gastric Cancer. Morphological Characteristics and Prognostic Value

The “cavitary” type of angiogenesis in patients with gastric cancer (GC) is described for the first time. Material and methods: The samples of tumour and adjacent gastric mucosa (GM) in 73 patients with GC who had undergone radical surgery were being studied. The sections were stained with hematoxylin and eosin (H&E) and immunohistochemically (IGH) using antibodies to CD34. Results: А new type of vessel formation consists of the appearance of cavitary structures (CS) in tumours and the adjacent GM, which are then lined by endothelial cells and merged into the blood vessels of the organ. We believe that the CS can be formed by means: 1) of the abruption of layers of epithelial cells (both normal and tumoral) from their underlying foundation and their desquamation into the lumen of the “obliterated” gastric glands (GG); 2) of the dilatation of the GG and thinning of their walls; 3) of the formation of “cavity” directly in the lamina propria of GM or in the tumoral stroma. It was noted that only the presence of multiple “cavitary” vessels (CV) of type-1 had been associated with the decrease of 3-year overall survival (OR=15,0, 95%CI=2,96-76,31) and relapse-free survival (OR=14,93, 95%CI=4,34-51,38). We also observed the improvement of the long-term outcomes in patients with GC having received antibacterial therapy (AT) before surgery that can be associated with its influence on the formation of CV type-1. Conclusion: The described new type of angiogenesis is of great clinical importance.
Comparison of factor VIII-related von Willebrand factor proteins prepared from human cryoprecipitate and factor VIII concentrate.

Both commercial factor VIII concentrate and cryoprecipitate have factor VIII coagulant activity and factor VIII antigen (VIIIR:Ag). but the concentrate lacks the von Willebrand activity (VIIIR:WF) found in the cryoprecipitate. In an effort to find a possible cause for this anomaly we compared the structures of VlllR:WF proteins responsible for the VllIR:Ag and VlllR:WF activities obtained from the two sources. Samples of cryoprecipitate and concentrate were chromatographed on agarose gel. and the resultant VIIIR:WF protein-rich void volume fractions were analyzed by firstand second-dimension sodium dodecyl sulfate gel electrophoresis. Proteins were first separated on a 1.5 % polyacrylamide-0.5 % agarose gel and then reduced and electrophoresed into a 3 % polyacrylamide-0.5 % agarose gel. VIIIR:WF protein from both cryoprecipitate and concentrate was multimeric. with polymers composed of M = 2.4 X 1 0 subunits. However, the multimers of the VIIIR:WF proteins from the two sources differed in average molecular weight and structure. Cryoprecipitate VIIIR:WF multimers were predominantly in the molecular weight range above 5 X 1 0 d and were uniformly separated from each other by increments of M = 6.5 X 10 . In contrast, concentrate VIIIR:WF multimers were relatively smaller, predominantly in the molecular weight range from 1.4 X 10d to 5 X 10d. The polymeric bands were separated from each other by spaces equivalent to approximately Mr = 5 X 1 0 alternating with distances of M = 2.5 X 1 These differences in molecular weight and structure are possible causes for the functional property demonstrated here that VlllR:WF protein from cryoprecipitate had 2.6 times more VlllR:WF activity per M = 2.4 X subunit than VIIIR:WF protein from concentrate.
The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort

Purpose To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. Methods SLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. Results 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001for mild-moderate). Conclusions The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.
Broom: Sweeping Out Garbage Collection from Big Data Systems

Many popular systems for processing "big data" are implemented in high-level programming languages with automatic memory management via garbage collection (GC). However, high object churn and large heap sizes put severe strain on the garbage collector. As a result, applications underperform significantly: GC increases the runtime of typical data processing tasks by up to 40%. We propose to use region-based memory management instead of GC in distributed data processing systems. In these systems, many objects have clearly defined lifetimes. Hence, it is natural to allocate these objects in fate-sharing regions, obviating the need to scan a large heap. Regions can be memory-safe and could be inferred automatically. Our initial results show that region-based memory management reduces emulated Naiad vertex runtime by 34% for typical data analytics jobs.
Natural history of left ventricular performance at rest and during exercise after aortic valve replacement for aortic regurgitation.

Previous studies of left ventricular performance in aortic regurgitation uniformly indicate improvement within the year after aortic valve replacement but differ regarding the likelihood of additional later improvement. To resolve this difference, to more precisely define the pattern of postoperative left ventricular performance variation, and to assess the impact of valve replacement on ejection fraction during exercise, we evaluated radionuclide cineangiograms obtained annually or nearly annually for approximately 5 years in 21 prospectively studied patients who had undergone valve replacement for aortic regurgitation. Ejection fraction rose from less than 8 months before operation to 5-11 (average 7) months after operation and continued to rise for 1 additional year (rest) and 2 additional years (exercise) before reaching a stable plateau until the final study 54-72 (average 63) months postoperatively. Mean ejection fractions at rest were 45% preoperatively, 50% less than 1 year postoperatively (p = 0.12), 54% at year 1-2 (p = 0.01 versus less than 1 year), 56% at year 2-3 (NS versus year 1-2) and year 4-6 (NS versus year 1-2 or 2-3), and during exercise were 39% preoperatively, 49% less than 1 year postoperatively (p less than 0.01), 54% at year 1-2 (p less than 0.01 versus less than 1 year, NS versus year 2-3, p less than 0.05 versus year 4-6), 60% at year 2-3, and 61% at year 4-6 (NS versus year 2-3). Late improvement was found most consistently among patients with relatively depressed performance before operation. (ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacological Analysis and Structure Determination of 7-Methylcyanopindolol–Bound β1-Adrenergic Receptor

Comparisons between structures of the β1-adrenergic receptor (AR) bound to either agonists, partial agonists, or weak partial agonists led to the proposal that rotamer changes of Ser5.46, coupled to a contraction of the binding pocket, are sufficient to increase the probability of receptor activation. (RS)-4-[3-(tert-butylamino)-2-hydroxypropoxy]-1H-indole-2-carbonitrile (cyanopindolol) is a weak partial agonist of β1AR and, based on the hypothesis above, we predicted that the addition of a methyl group to form 4-[(2S)-3-(tert-butylamino)-2-hydroxypropoxy]-7-methyl-1H-indole-2-carbonitrile (7-methylcyanopindolol) would dramatically reduce its efficacy. An eight-step synthesis of 7-methylcyanopindolol was developed and its pharmacology was analyzed. 7-Methylcyanopindolol bound with similar affinity to cyanopindolol to both β1AR and β2AR. As predicted, the efficacy of 7-methylcyanopindolol was reduced significantly compared with cyanopindolol, acting as a very weak partial agonist of turkey β1AR and an inverse agonist of human β2AR. The structure of 7-methylcyanopindolol–bound β1AR was determined to 2.4-Å resolution and found to be virtually identical to the structure of cyanopindolol-bound β1AR. The major differences in the orthosteric binding pocket are that it has expanded by 0.3 Å in 7-methylcyanopindolol–bound β1AR and the hydroxyl group of Ser5.46 is positioned 0.8 Å further from the ligand, with respect to the position of the Ser5.46 side chain in cyanopindolol-bound β1AR. Thus, the molecular basis for the reduction in efficacy of 7-methylcyanopindolol compared with cyanopindolol may be regarded as the opposite of the mechanism proposed for the increase in efficacy of agonists compared with antagonists.
Coastal Altimetry Products in the Strait of Gibraltar

This paper analyzes the availability and accuracy of coastal altimetry sea level products in the Strait of Gibraltar. All possible repeats of two sections of the Envisat and AltiKa ground-tracks were used in the eastern and western portions of the strait. For Envisat, along-track sea level anomalies (SLAs) at 18-Hz posting rate were computed using ranges from two sources, namely, the official Sensor Geophysical Data Records (SGDRs) and the outputs of a coastal waveform retracker, the Adaptive Leading Edge Subwaveform (ALES) retracker; in addition, SLAs at 1 Hz were obtained from the Centre for Topographic studies of the Ocean and Hydrosphere (CTOH). For AltiKa, along-track SLA at 40 Hz was also computed both from SGDR and ALES ranges. The sea state bias correction was recomputed for the ALES-retracked Envisat SLA. The quality of these altimeter products was validated using two tide gauges located on the southern coast of Spain. For Envisat, the availability of data close to the coast depends crucially on the strategy followed for data screening. Most of the rejected data were due to the radar instrument operating in a low-precision nonocean mode. We observed an improvement of about 20% in the accuracy of the Envisat SLAs from ALES compared to the standard (SGDR) and the reprocessed CTOH data sets. AltiKa shows higher accuracy, with no significant differences between SGDR and ALES. The use of products from both missions allows longer times series, leading to a better understanding of the hydrodynamic processes in the study area.
Natural History of Streptococcus sanguinis in the Oral Cavity of Infants: Evidence for a Discrete Window of Infectivity

ABSTRACT The heterogeneous group of oral bacteria within the sanguinis (sanguis) streptococci comprise members of the indigenous biota of the human oral cavity. While the association of Streptococcus sanguinis with bacterial endocarditis is well described in the literature, S. sanguinis is thought to play a benign, if not a beneficial, role in the oral cavity. Little is known, however, about the natural history of S. sanguinis and its specific relationship with other oral bacteria. As part of a longitudinal study concerning the transmission and acquisition of oral bacteria within mother-infant pairs, we examined the initial acquisition of S. sanguinis and described its colonization relative to tooth emergence and its proportions in plaque and saliva as a function of other biological events, including subsequent colonization with mutans streptococci. A second cohort of infants was recruited to define the taxonomic affiliation of S. sanguinis. We found that the colonization of the S. sanguinis occurs during a discrete “window of infectivity” at a median age of 9 months in the infants. Its colonization is tooth dependent and correlated to the time of tooth emergence; its proportions in saliva increase as new teeth emerge. In addition, early colonization of S. sanguinis and its elevated levels in the oral cavity were correlated to a significant delay in the colonization of mutans streptococci. Underpinning this apparent antagonism between S. sanguinis and mutans streptococci is the observation that after mutans streptococci colonize the infant, the levels of S. sanguinis decrease. Children who do not harbor detectable levels of mutans streptococci have significantly higher levels of S. sanguinis in their saliva than do children colonized with mutans streptococci. Collectively, these findings suggest that the colonization of S. sanguinis may influence the subsequent colonization of mutans streptococci, and this in turn may suggest several ecological approaches toward controlling dental caries.
A distributed self-stabilizing algorithm for argumentation

We propose a distributed approach to argumentation in which arguments are constructed by asynchronous processes which compute their own defeat status on the basis of local information. We present a self-stabilizing algorithm for the computation of defeat status, along with a proof of its correctness. The proposed approach introduces a remarkable flexibility in the management of argumentation activity with respect to a centralized approach. Moreover it is in line with the evolution of autonomous agents architectures, one of the main application fields of argumentation systems.
Poly Cystic Ovarian Syndrome: An Updated Overview

Poly Cystic Ovarian Syndrome (PCOS) is one of the most common metabolic and reproductive disorders among women of reproductive age. Women suffering from PCOS present with a constellation of symptoms associated with menstrual dysfunction and androgen excess, which significantly impacts their quality of life. They may be at increased risk of multiple morbidities, including obesity, insulin resistance, type II diabetes mellitus, cardiovascular disease (CVD), infertility, cancer, and psychological disorders. This review summarizes what the literature has so far provided from guidelines to diagnosis of PCOS. It will also present a general overview about the morbidities associated with this disease, specifically with its more severe classic form. Finally, the review will stress on the various aspects of treatment and screening recommendations currently used in the management of this condition.
THD Reduction of Distribution System Based on ASRFC and HVC Method for SVC under EV Charger Condition for Power Factor Improvement

Electric vehicles (EVs) have been gaining popularity in recent years due to growing concerns about fuel depletion and increasing petrol prices. Random uncoordinated charging of multiple EVs at residential distribution feeders with moderate penetration levels is expected in the near future. This paper describes a high performance voltage controller for the EVs charging system, and proposes a scheme of asymmetric synchronous reference frame controller (ASRFC) in order to compensate for the voltage distortions and unbalance distribution system due to EVs charger. This paper explores the power factor of distribution and residential network under random EVs charger on the bus load. ASRFC and harmonic voltage compensator (HVC) are employed for static VAR compensator (SVC) in this paper. The proposed scheme can improve the power factor and total harmonic distortion (THD) of the smart grid due to the EVs charger in grid. The effectiveness of the scheme was investigated and verified through computer simulations of a 22.9-kV grid.