Miracle-dz/UniFAR-FTUs huggingface dataset:
Compensation of DNA Stabilization and Destabilization Effects Caused by Cisplatin is Partially Disturbed in Alkaline Medium

Abstract Binding of the antitumor compound cisplatin to DNA locally distorts the double helix. These distortions correlate with a decrease in DNA melting temperature (Tm). However, the influence of cisplatin on DNA stability is more complex because it decreases the DNA charge density. In this way, cisplatin increases the melting temperature and partially compensates for the destabilizing influence of structural distortions. The stabilization is stronger at low Na+ ion concentration. Due to this compensation, the total decrease in the DNA melting temperature after cisplatin binding is much lower than the decrease caused by the distortions themselves, especially at low [Na+]. It is shown in this study that, besides Na+ concentration, pH also strongly influences the value of a change in the melting temperature caused by cisplatin. In alkaline medium (pH=10.5–10.8), a fall in the melting temperature caused by platination is enhanced several times with respect to neutral medium. Such a stronger drop in Tm is explained by a decrease in pK values of base pairs caused by lowering the charge density under platination that facilitates proton release. At neutral pH, the proton release is low for both control and platinated DNA and does not influence the melting behavior. Therefore, lowering in the charge density under platination, besides stabilization, gives additional destabilization just in alkaline medium. Destabilization caused by structural distortions due to this pH induced compensation of stabilizing effect is more pronounced. In the presence of carbonate ion, destabilization caused by high pH value is strengthened. As a decrease in DNA charge density, interstrand crosslinking caused by cisplatin also increases the DNA stability due to loss in the entropy of the melted state. However, computer modeling of DNA stability demonstrates that interstrand crosslinks formed by cisplatin do not stabilize long DNA. It is shown that the increase in Tm caused by interstrand crosslinking itself is compensated for by a local destabilization of the double helix at the sites of location of interstrand crosslinks formed by cisplatin.
Involvement of Microglial P2Y12 Signaling in Tongue Cancer Pain

To elucidate if microglial P2Y12 receptor (P2Y12R) mechanisms are involved in the trigeminal spinal subnucleus caudalis (Vc; also known as the medullary dorsal horn) in intraoral cancer pain, we developed a rat model of tongue cancer pain. Squamous cell carcinoma (SCC) cells were inoculated into the tongue of rats; sham control rats received the vehicle instead. Nociceptive behavior was measured as the head-withdrawal reflex threshold (HWRT) to mechanical or heat stimulation applied to the tongue under light anesthesia. On day 14 after the SCC inoculation, activated microglia and P2Y12R expression were examined immunohistochemically in the Vc. The HWRT was also studied in SCC-inoculated rats with successive intra–cisterna magna (i.c.m.) administration of specific P2Y12R antagonist (MRS2395) or intraperitoneal administration of minocycline, a microglial activation inhibitor. Tongue cancer was histologically verified in SCC-inoculated rats, within which the HWRT to mechanical stimulation of the tongue was significantly decreased, as compared with that of vehicle-inoculated rats, although the HWRT to heat stimulation was not. Microglia was strongly activated on day 14, and the administration of MRS2395 or minocycline reversed associated nocifensive behavior and microglial activation in SCC-inoculated rats for 14 d. The activity of Vc wide dynamic range nociceptive neurons was also recorded electrophysiologically in SCC-inoculated and sham rats. Background activity and noxious mechanically evoked responses of wide dynamic range neurons were significantly increased in SCC-inoculated rats versus sham rats, and background activity and mechanically evoked responses were significantly suppressed following i.c. m. administration of MRS2395 in SCC-inoculated rats as compared with sham. The present findings suggest that SCC inoculation that produces tongue cancer results in strong activation of microglia via P2Y12 signaling in the Vc, in association with increased excitability of Vc nociceptive neurons, reflecting central sensitization and resulting in tongue mechanical allodynia.
Effect of tendon hydrogel on healing of tendon injury

Hand trauma arising from postoperative acute or chronic tendon injuries leads to delayed union and is one of the greatest challenges in clinical practice. The present study hypothesized that an extracellular matrix hydrogel made from tendons can promote tendon healing and improve tissue regeneration. To verify this, 36 Wistar rats were subjected to bilateral full-thickness injury of their Achilles tendons, starting from the heel bone along the center line to remove a segment of 5 mm in length and 0.5 mm in width. On the sites of injury, hydrogel was injected on one side, while the contralateral side was injected with an equal volume of normal saline. At 2, 4 and 8 weeks after the operation, bilateral tendons were subjected to biomechanical tests to determine the ultimate failure load, tensile strength and toughness, and cross-sectional slices of the tendons were subjected to histological analysis. The results indicated that after 2 weeks, the hydrogel and control group showed no significant difference in terms of ultimate load (P=0.15) ultimate tensile stress (P=0.42) and toughness (P=0.76). At 4 weeks following surgery, the failure load in the hydrogel group was significantly higher than that in the control group (74.8±14.2 vs. 58.4±11.6; P=0.02), while there were no significant differences in the ultimate tensile stress (P=0.63) and toughness (P=0.08). At 8 postoperative weeks, the abovementioned parameters showed no significant difference between the groups (P=0.15, 0.39 and 0.75, respectively). In conclusion, the tendon-derived extracellular matrix hydrogel was able to significantly improve tendon strength at 4 weeks after injury in terms of increasing the ultimate failure load. Hydrogel applied immediately after tendon injury can enhance the type-I collagen content. The present study therefore provided a basis for further exploration of the application of extracellular matrix hydrogel to promote tendon healing in the clinic.
Aberrant Gating of Photic Input to the Suprachiasmatic Circadian Pacemaker of Mice Lacking the VPAC2 Receptor

VIP acting via the VPAC2 receptor is implicated as a key signaling pathway in the maintenance and resetting of the hypothalamic suprachiasmatic nuclei (SCN) circadian pacemaker; circadian rhythms in SCN clock gene expression and wheel-running behavior are abolished in mice lacking the VPAC2 receptor (Vipr2–/–). Here, using immunohistochemical detection of pERK (phosphorylated extracellular signal-regulated kinases 1/2) and c-FOS, we tested whether the gating of photic input to the SCN is maintained in these apparently arrhythmic Vipr2–/– mice. Under light/dark and constant darkness, spontaneous expression of pERK and c-FOS in the wild-type mouse SCN was significantly elevated during subjective day compared with subjective night; no diurnal or circadian variation in pERK or c-FOS was detected in the SCN of Vipr2–/– mice. In constant darkness, light pulses given during the subjective night but not the subjective day significantly increased expression of pERK and c-FOS in the wild-type SCN. In contrast, light pulses given during both subjective day and subjective night robustly increased expression of pERK and c-FOS in the Vipr2–/– mouse SCN. Although photic stimuli activate intracellular pathways within the SCN of Vipr2–/– mice, they do not engage the core clock mechanisms. The absence of photic gating, together with the general lack of overt rhythms in circadian output, strongly suggests that the SCN circadian pacemaker is completely dysfunctional in the Vipr2–/– mouse.
Expression of Yes-Associated Protein in Cervical Squamous Epithelium Lesions

Objective Yes-associated protein (YAP) was defined as a candidate oncogene in multiple cancers. Yet, the role of YAP in cervical cancer is largely unknown. The aim of this study was to determine whether YAP could be used as a predictive biomarker in cervical precancerous lesions. Methods Immunohistochemical analysis of YAP expression was performed in 10 chronic cervicitis, 49 cervical intraepithelial neoplasia (CIN) 1, 55 CIN 2, 34 CIN 3, and 32 cervical squamous cell carcinoma (SCC) samples. Human papillomavirus (HPV) was detected by HPV genotype detection kit in 70 cases including 10 chronic cervicitis cases, 13 CIN 1 cases, 19 CIN 2 cases, 14 CIN 3 cases, and 14 SCC cases. Furthermore, the relationship between YAP expression and HPV integration status was analyzed using Spearman rank correlation coefficient test. Result Samples of chronic cervicitis had negative or weak expression of YAP in cytoplasm. In the CIN 1 group, YAP expression was primarily confined to the lower third part of squamous epithelia or basal layer, whereas higher-grade CIN (2 and 3) and SCC groups had a strong nuclear expression of YAP. The expression levels of YAP in chronic cervicitis and CIN 1 were significantly lower compared to those in higher-grade CIN and SCC. Moreover, YAP expression was correlated with HPV integration status. Most high-risk HPV(+)/YAP(+) cases were found in the CIN 3 and SCC groups. Conclusion This study suggested that YAP could function as a predictive marker in CIN and cervical cancer. YAP expression, in combination of HPV, might facilitate the identification of precancerous cervical lesions.
Design Criteria of Low-Power Oscillators for Consumer-Grade MEMS Resonant Sensors

This paper discusses the constraints in the design of circuits for microelectromechanical systems (MEMS) resonant sensors in consumer applications, presents a novel integrated circuit implementation, and shows that this approach can be competitive with respect to the mostly used capacitive readout. From a circuit design perspective, it is shown how the large equivalent resistance typical of MEMS resonators, their operation close to mechanical nonlinearity, and the effect of feedthrough capacitances on the oscillating loop constrain the power requirements of the driving/readout electronics. As a case study, a resonant accelerometer built in an industrial process is coupled to a suitably designed transimpedance amplifier with a low-power “hard limiter. ” The performance shown in terms of linearity across the measurement range (±8 g), minimum measurable acceleration (1 mg with a readout bandwidth of 100 Hz), and power consumption (≈ 100 μW per axis) is comparable to those of state-of-the-art capacitive inertial sensors.
Evaluating the Extended Refactoring Guidelines

Refactoring is a process that improves the internal structure of a program without changing its externally observable behavior. On the contrary, in many cases refactoring support for java outputs semantically non-equivalent code after refactoring. Also, the research on refactoring has mostly focused on restructuring a class, its parent and child classes only. However, refactoring will not be complete without updating other components in the program that may be impacted because of this change. In particular, clients and test classes associated with the restructured classes may be affected by this change and hence must be updated accordingly. In this work, we have identified the exact nature of changes required in these effected components and the elements contained in them. Using this information we have developed extended refactoring guidelines that address semantic violations of program behavior during refactoring. We also report our findings from an experiment performed to judge the usability and effectiveness of the extended guidelines for Move Method refactoring.
Spectrum of Clinically Relevant Acremonium Species in the United States

ABSTRACT Some species in the polyphyletic fungal genus Acremonium are important opportunist pathogens. Determining the actual spectrum of species and their incidence in the clinical setting, however, has long been hampered because of the difficulties encountered in phenotypic species-level identification. The goal of this study was to re-identify a large number of clinical isolates morphologically and to confirm the identifications by comparing sequences of the internal transcribed spacer region of the rRNA gene of these isolates to those of type or reference strains of well-known Acremonium species. Of the 119 isolates referred to a United States reference laboratory under the name Acremonium, only 75 were identified morphologically as belonging to that genus. The remainder (44 isolates) were identified as belonging to other morphologically similar genera. The Acremonium clinical isolates were related to species of Hypocreales, Sordariales, and of an incertae sedis family of ascomycetes, Plectosphaerellaceae. A total of 50 of the 75 Acremonium isolates (67%) could be identified by molecular means, the prevalent species being Acremonium kiliense (15 isolates), A. sclerotigenum-A. egyptiacum (11 isolates), A. implicatum (7 isolates), A. persicinum (7 isolates), and A. atrogriseum (4 isolates). One of the most interesting findings of our study was that we identified several species among this large collection of clinical isolates that had not previously been reported from human infections, and we failed to confirm other Acremonium species, such as A. potronii, A. recifei, and A. strictum, that had been considered significant. The most common anatomic sites for Acremonium isolates were the respiratory tract (41.3%), nails (10.7%), and the eye (9.3%). Antifungal susceptibility testing demonstrated high MICs for all agents tested, except for terbinafine. Since numerous isolates could not be identified, we concluded that the list of opportunistic Acremonium species is far from be complete and that a considerable number of additional species will be discovered.
Birth Outcomes in Women with Inflammatory Bowel Disease: Effects of Disease Activity and Drug Exposure

Background:Ulcerative colitis (UC) and Crohn's disease (CD) have been associated with increased risks of adverse birth outcomes. Disease activity and drug exposure may contribute to the association. Methods:A cohort from the Swedish health registers including 470,110 singleton births in Sweden from July 2006 to December 2010; 1833 to women with UC and 1220 to women with CD. Birth outcomes for women with UC and CD were compared with outcomes among those without disease. Diseased women were categorized by drug exposure, need of surgery, and hospital admissions as (1) no disease activity and (2) stable or (3) flaring disease. Logistic regression was used to calculate odds ratios with adjustments (aOR) for maternal age, parity, smoking status, body mass index, and comorbidity. Results:There were increased risks of preterm birth for both UC (aOR, 1.78; 95% confidence interval [CI], 1.49–2.13) and CD (aOR, 1.65; 95% CI, 1.33–2.06). Risks were more pronounced in women with flaring disease during pregnancy. Risks of small for gestational age, low Apgar score, and hypoglycemia were also increased. The risk of stillbirth was elevated in women with CD, particularly among those with flaring disease (aOR, 4.48; 95% CI, 1.67–11.90). Thiopurine exposure increased risks for preterm birth, both in women with stable (aOR, 2.41; 95% CI, 1.05–5.51) and with flaring disease (aOR, 4.90; 95% CI, 2.76–8.69). Conclusions:Women with UC and CD are at increased risk of adverse birth outcomes, such as stillbirth, growth restriction, and preterm birth, particularly when they suffer from flares throughout pregnancy. Thiopurine exposure seems to further increase risks, independently of disease activity.
Interaction of membrane‐bound islet amyloid polypeptide with soluble and crystalline insulin

Islet amyloid polypeptide (IAPP, also known as amylin) is the major protein component of pancreatic amyloid fibers in type II diabetes and is normally cosecreted with insulin from the β‐cells of the pancreas. IAPP forms amyloid fibrils rapidly at concentrations well below those found in vivo, yet progression of type II diabetes occurs over many years. Insulin, a known inhibitor of IAPP fibrillogenesis, exists as a dense crystalline or near‐crystalline core in the secretory vesicle, while IAPP localizes to the region between the crystal and the secretory vesicle membrane. In vitro, IAPP fibrillogenesis is both accelerated by lipid membranes and inhibited by monomeric insulin. In this work, we investigate insulin–IAPP–lipid interactions in vitro under conditions chosen to approximate native secretory vesicle physiology and the amyloid disease state. The effect of insulin on IAPP fibrillogenesis is investigated using fluorescence spectrometry. Additionally, interactions of IAPP and lipids with crystalline insulin are studied using fluorescence microscopy. We find that, while soluble states of insulin and IAPP do not interact significantly, large assemblies of either insulin (crystals) or IAPP (fibers) can lead to stable IAPP–insulin interactions. The results raise the possibility of multiple physiological interactions between these two β‐cell hormones.
Représentation alternative des canaux à relais gaussiens à travers un noeud virtuel

Dans cette communication, nous montrons que sous une contrainte de puissance globale a repartir entre les noeuds, les bornes superieures et inferieures decode-and-forward de la capacite d'un canal a relais coherent sont les memes que celle d'un canal a relais non-coherent equivalent. Cette relation d'equivalence existe pour les modeles full-duplex et half-duplex, ou le relais ne peut ecouter et transmettre simultanement. L'expression des bornes de capacite etant grandement simplifiee, il est possible en utilisant ce resultat d'extraire tres simplement une repartition de puissance optimale sous forme analytique. Cette allocation nous amene a identifier un critere de selection de relais original, dont nous evaluons les performances en le comparant a ceux utilises dans la litterature.
Compartmentalized Expression of Th1 and Th17 Cytokines in Pediatric Inflammatory Bowel Diseases

Background: Interleukin (IL)‐23, IL‐17A, IL‐17F, and interferon‐gamma (IFN‐&ggr;) are important mediators of inflammatory colitis and are potential therapeutic targets in inflammatory bowel disease (IBD). Their expression profile in the different parts of normal noninflammatory intestine is unclear and their changes during pathology have not yet been addressed in pediatric IBD patients. Methods: We quantified the transcriptional expression of IL‐23, IL‐12, IL‐17A, IL‐17F, IL‐6, and IL‐10 in healthy, noninflammatory duodenum, ileum, and colon and in inflamed and noninflamed biopsies of pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). Results: In healthy tissue, expression of IL‐17A is highest in the ileum, with IFN‐&ggr; expression lowest in the colon. Compared to healthy sections, CD patients displayed increased IL‐12p35 and IFN‐&ggr; levels in noninflamed ileum and colon, respectively. Modifications of cytokine expression between noninflamed and inflamed tissues was characterized by increased IL‐17A in UC colon, IFN‐&ggr; in CD colon, and IL‐17A, IFN‐&ggr; and IL‐6 in CD ileum. Elevated IL‐17A levels were positively correlated with IFN‐&ggr; in both inflammatory CD and UC but IL‐17A and IFN‐&ggr; were correlated with IL‐23p19 in CD ileum only. Conclusions: The expression of Th1 and Th17 cytokines varies along the intestine, indicating local specific regulation mechanisms. However, the cytokine expression patterns in the same tissue depends on the pathology, with a Th1 or a Th17 profile in the colon of CD and UC patients, respectively, and a Th1/Th17 profile in the ileum of CD patients. This indicates overlapping but distinct immune mechanisms driving intestinal inflammation in these two pathologies. (Inflamm Bowel Dis 2011)
The economic cost of invasive pneumococcal disease and the potential for reduction by vaccination in an adult population in South Yorkshire.

Sir, Risk factors for invasive pneumococcal disease (IPD) permit targeted immunization of adults with a 23-valent capsular polysaccharide of moderate efficacy.1,,2 We identified 553 adult cases of IPD in Sheffield between 1992 and 2000, identified all 230 cases admitted to the Royal Hallamshire Hospital, Sheffield, and retrospectively estimated the economic costs and potential vaccine impact on IPD. Of 206 cases with analysable medical records, 143 (77%) had prior indications for vaccination per UK guidelines. There were 40 deaths (21%). At our location, 48/50 (96%) strains causing IPD in adults were contained in the pneumococcal polysaccharide vaccine (H.K. Parsons, unpublished data). The costing took an NHS perspective, including vaccination costs limited …
Colorectal liver metastases with a disrupted circadian rhythm phase shift the peripheral clock in liver and kidney

Circadian clock genes regulate 10–15% of the transcriptome, and might function as tumor suppressor genes. Relatively little is known about the circadian clock in tumors and its effect on surrounding healthy tissues. Therefore, we compared the 24‐hr expression levels of key circadian clock genes in liver and kidney of healthy control mice with those of mice bearing C26 colorectal tumor metastases in the liver. Metastases were induced by injection of C26 colorectal carcinoma cells into the spleen. Subsequently, tumor, liver and kidney tissue was collected around the clock to compare circadian rhythmicity. Expression levels of five clock genes (Rev‐Erbα, Per1, Per2, Bmal1 and Cry1) and three clock‐controlled genes (CCGs; Dbp, p21 and Wee1) were determined by qRT‐PCR. Liver and kidney tissue of healthy control mice showed normal 24‐hr oscillations of all clock genes and CCGs, consistent with normal circadian rhythmicity. In colorectal liver metastases, however, 24‐hr oscillations were completely absent for all clock genes and CCGs except Cry1. Liver and kidney tissue of tumor‐bearing mice showed a shift in clock periodicity relative to control mice. In the liver we observed a phase advance, whereas in the kidney the phase was delayed. These data show that hepatic metastases of C26 colon carcinoma with a disrupted circadian rhythm phase shift liver and kidney tissue clocks, which strongly suggests a systemic effect on peripheral clocks. The possibility that tumors may modify peripheral clocks to escape from ordinary circadian rhythms and in this way contribute to fatigue and sleep disorders in cancer patients is discussed.
Statistical Markovian Data Modeling for Natural Language Processing

BSTRACT Markov chain theory is a popular statistical tool in applied probability that is quite useful in modelling real-world computing applications. Over the past years; there has been grown interest to employ Markov chain theory in statistical learning of temporal (i.e. time series) data. A wide range of applications found to utilize Markov concepts; such applications include computational linguists, image processing, communications, bioinformatics, finance systems, etc . In fact, Markov processes based research applied with great success in many of the most efficient natural language processing (NLP) tools. Hence, this paper explores the Markov chain theory and its extension hidden Markov models (HMM) in (NLP) applications. This paper also presents some aspects related to Markov chains and HMM such as creating transition and observation matrices, calculating data sequence probabilities, extracting the hidden states, and profile HMM.