Miracle-dz/UniFAR-FTUs huggingface dataset:
Hardness of Continuous Local Search: Query Complexity and Cryptographic Lower Bounds

Local search proved to be an extremely useful tool when facing hard optimization problems (e.g., via the simplex algorithm, simulated annealing, or genetic algorithms). Although powerful, it has its limitations: there are functions for which exponentially many queries are needed to find a local optimum. In many contexts the optimization problem is defined by a continuous function, which might offer an advantage when performing the local search. This leads us to study the following natural question: How hard is continuous local search? The computational complexity of such search problems is captured by the complexity class CLS (Daskalakis and Papadimitriou SODA'11) which is contained in the intersection of PLS and PPAD, two important subclasses of TFNP (the class of NP search problems with a guaranteed solution). In this work, we show the first hardness results for CLS (the smallest non-trivial class among the currently defined subclasses of TFNP). Our hardness results are in terms of black-box (where only oracle access to the function is given) and white-box (where the function is represented succinctly by a circuit). In the black-box case, we show instances for which any (computationally unbounded) randomized algorithm must perform exponentially many queries in order to find a local optimum. In the white-box case, we show hardness for computationally bounded algorithms under cryptographic assumptions. Our results demonstrate a strong conceptual barrier precluding design of efficient algorithms for solving local search problems even over continuous domains. As our main technical contribution we introduce a new total search problem which we call E nd - of -M etered -L ine . The special structure of E nd - of -M etered -L ine enables us to: (1) show that it is contained in CLS, and (2) prove hardness for it both in the black-box and the white-box setting.
Rôle de l’élasticité du substrat sur des cellules épithéliales en cours de division et sur la régulation d’activités nucléaires

Les forces mecaniques ont une incidence dans la croissance et la morphologie des tissus. Le cytosquelette et les contacts focaux ont un role structurel sur la cellule. Une premiere question etait de determiner si l’elasticite du substrat modifie ces organisations, et si elles sont indispensables au maintien d’activites nucleaires de cellules epitheliales PtK2. Le module de Young, E du substrat varie de 0 a 500kPa. Les fibres d’actine et les contacts focaux sont absents pour une elasticite de 0 et 50kPa. La replication est egalement inhibee. A partir de 200 kPa, Rac1 est a l’origine de la formation des contacts focaux, des fibres d’actine et de l’initiation de la replication. Les films de 50kPa permettent l’activite de la transcription. Ces resultats revelent une regulation selective et decouplee de l’elasticite du substrat sur la replication et la transcription de cellules PtK2. La deuxieme question portait sur le role de l’elasticite du substrat lors de la division cellulaire. La sortie de mitose est reduite pour 50kPa et presente des instabilites chromosomiques entrainant l’apoptose. L’elasticite 50kPa provoque d’autres alterations qui sont, un faible engagement des integrines αv et une destructuration du fuseau mitotique. Aux faibles elasticites (50kPa), les cellules subissent deux points de controle : 1) en mitose par la formation d’instabilites chromosomiques et par l’inhibition de la cytokinese, 2) en interphase par l’inhibition de la replication. L’elasticite du substrat pourrait exercer, in vivo, une barriere naturelle soit pour des cellules a fortes motilites ou pour des cellules non migratoires confrontees a des modifications mecaniques de leurs environnements.
Pancreatic cytopathology: a practical approach and review.

CONTEXT Pancreatic cytopathology plays an important role in the diagnosis and management of patients with solid and cystic lesions of the pancreas. OBJECTIVE To serve as a practical guide to pancreatic cytopathology for the practicing pathologist. Data Sources. -A comprehensive assessment of the medical literature was performed. CONCLUSIONS We review pancreatic cytopathology, with specific discussions of its role in patient management, specimen types and specimen processing, specific diagnostic criteria, and the use of ancillary testing and advanced techniques.
Application of Serum ELAVL4 (HuD) Antigen Assay for Small Cell Lung Cancer Diagnosis.

BACKGROUND/AIM The ELAVL4 (HuD) is a neuron-specific RNA-binding protein expressed in 100% of small cell lung cancer (SCLC) cells and over 50% of neuroblastoma cells. The aim of this study was to investigate the serum HuD concentration in SCLC patients and the possibility of its utilization as a biomarker of small cell lung cancer. MATERIALS AND METHODS Our study included 47 SCLC cases and 29 normal controls. Indirect competitive inhibition ELISA method was established to detect HuD antigen of serum samples. To design the ELISA system, purified antigen and real positive and negative serum samples were used, and checkerboard titration was performed. The value of current serum biomarkers (Pro-GRP, NSE, CYFRA21-1 and CEA) was obtained from a clinical laboratory. RESULTS The HuD antigen concentration in the SCLCgroup was significantly higher than that in the normal group (p<0.01). The cut-off value, specificity and sensitivity were 60 ng/ml, 89.7% and 74.5%, respectively. The best linear range was 9.75~600 ng/ml. The sensitivity of the HuD-ELISA assay was much better than the current biomarkers-CEA, NSE and pro-GRP. Also,it was equal to or better than the combined use of two or three indicators. CONCLUSION The high titres of HuD in SCLC patients and preferable consistency suggested that HuD may serve as a potential diagnostic criterium for SCLC and may serve as a marker of disease progression.
Network capacity allocation for traffic with time priorities

The packet switching techniques are undergoing evolution. The conventional ‘best effort’ approach will no longer be the dominant service. The next generation of IP networks must provide QoS to customers. Inadequacy is obvious when the conventional capacity allocation (CA) models are applied to the new IP architecture. In this paper, we propose several CA models that characterize: (1) the service priority scheme; (2) the service preemption scheme; and (3) the non‐Poisson traffic in which the packets follow heavy tailed distributions. Copyright © 2003 John Wiley & Sons, Ltd.
Nucleosome hopping and sliding kinetics determined from dynamics of single chromatin fibers in Xenopus egg extracts

Chromatin function in vivo is intimately connected with changes in its structure: a prime example is occlusion or exposure of regulatory sequences via repositioning of nucleosomes. Cell extracts used in concert with single-DNA micromanipulation can control and monitor these dynamics under in vivo-like conditions. We analyze a theory of the assembly–disassembly dynamics of chromatin fiber in such experiments, including effects of lateral nucleosome diffusion (“sliding”) and sequence positioning. Experimental data determine the force-dependent on- and off-rates as well as the nucleosome sliding diffusion rate. The resulting theory simply explains the very different nucleosome displacement kinetics observed in constant-force and constant-pulling velocity experiments. We also show that few-piconewton tensions comparable to those generated by polymerases and helicases drastically affect nucleosome positions in a sequence-dependent manner and that there is a long-lived structural “memory” of force-driven nucleosome rearrangement events.
Hyperbolic Distance Matrices

Hyperbolic space is a natural setting for mining and visualizing data with hierarchical structure. In order to compute a hyperbolic embedding from comparison or similarity information, one has to solve a hyperbolic distance geometry problem. In this paper, we propose a unified framework to compute hyperbolic embeddings from an arbitrary mix of noisy metric and non-metric data. Our algorithms are based on semidefinite programming and the notion of a hyperbolic distance matrix, in many ways parallel to its famous Euclidean counterpart. A central ingredient we put forward is a semidefinite characterization of the hyperbolic Gramian---a matrix of Lorentzian inner products. This characterization allows us to formulate a semidefinite relaxation to efficiently compute hyperbolic embeddings in two stages: first, we complete and denoise the observed hyperbolic distance matrix; second, we propose a spectral factorization method to estimate the embedded points from the hyperbolic distance matrix. We show through numerical experiments how the flexibility to mix metric and non-metric constraints allows us to efficiently compute embeddings from arbitrary data.
A Hebrew Tree Bank Based on Cantillation Marks

In the Masoretic text of the Hebrew Bible (HB), the cantillation marks function like a punctuation system that shows the division and subdivision of each verse, forming a tree structure which is similar to the prosodic tree in modern linguistics. However, in the Masoretic text, the structure is hidden in a complicated set of diacritic symbols and the rich information is accessible only to a few trained scholars. In order to make the structural information available to the general public and to automatic processing by the computer, we built a tree bank where the hierarchical structure of each HB verse is explicitly represented in XML format. We coded the punctuation system in a context-tree grammar which was then used by a CYK parser to automatically generate trees for the whole HB. The results show that (1) the CFG correctly encoded the annotation rules and (2) the annotation done by the Masoretes is highly consistent.
Exposure of tumor necrosis factor‐α to luminal membrane of bovine brain capillary endothelial cells cocultured with astrocytes induces a delayed increase of permeability and cytoplasmic stress fiber formation of actin

Tumor necrosis factor‐α (TNF‐α), a proinflammatory cytokine, has long been known to be involved in the pathogenesis of central nervous system infections and of certain neurodegenerative diseases. However, the possible role of the blood‐brain barrier (BBB), the active interface between the blood circulation and brain tissue, remained unknown during these pathological conditions. In our in vitro reconstructed BBB model, 1‐hr exposure of recombinant human TNF‐α (in concentrations of 50, 250, and 500 U/ml, respectively) to the luminal membrane of bovine brain capillary endothelial cells (BBCEC) did not change significantly the transendothelia: flux of either sucrose (m.w. 342 Da), or inulin (m.w. 5 kDa) up to 4 hr (early phase), except for a slight decrease (P< 0.05) in sucrose permeation at 2–4 hr with the highest dose of TNF‐α On the other hand, at 16 hr after the 1‐hr challenge with TNF‐α (delayed phase) at all 3 concentrations, significant increase was induced in the permeability of BBCEC monolayers for both markers. These changes of permeability were accompanied by a selective reorganization of F‐actin filaments into stress fibers, while the intracellular distribution of vimentin remained similar to the control. These results suggest that BBCEC can respond directly to TNF‐α by a delayed increase of permeability and reorganization of actin filaments. ©1995 Wiley‐Liss, Inc.
Genetic variation among Pearl millet genotypes for yield and its components in semi-arid zone Sudan

Twelve genotypes of Pearl millet were evaluated under rain-fed conditions in a semi-arid zone of El Fasher Research Station, Sudan for two consecutive seasons (2010 and 2011). Genotypic and phenotypic variability, heritability in a broad sense and genetic advance were estimated in a randomized complete block design with four replications. High genotypic coefficient of variation, heritability estimate (above 95 %) and genetic advance were recorded for grain yield (kg/ha) followed by straw yield (kg/ha) in both seasons. A number of heads/plant expressed low genetic advance with low heritability in both seasons. Highly significant and significant different among genotypes were found for all characters except number of heads/plant was observed non-significant. The high yielding genotypes were Dembi (Yellow), Sudan1 and SADC (Long) with grain yields of 499.8, 424.9 and 421.5 kg/ha, respectively. Grain yield kg/ha was significant and positively correlated with straw yield (kg/ha), plant height, number of heads/plant and 1000grain weight, while significant and negative correlated with days to 95% maturity. Therefore, straw yield (kg/ha), plant height, 1000grain weight, days to 95% maturity and number of heads/plant to be the important characters which would be used in selection for Pearl millet improvement. The promising genotypes identified in this study could provide valuable sources of resistance to climatechange-related stresses and for other consequent breeding activities in pearl millet improvement.
Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways

Malignant peripheral nerve sheath tumour (MPNST) is a rare malignancy accounting for 3–10% of all soft tissue sarcomas. Most MPNSTs arise in association with peripheral nerves or deep neurofibromas and may originate from neural crest cells, although the specific cell of origin is uncertain. Approximately half of MPNSTs occur in the setting of neurofibromatosis type 1 (NF1), an autosomal dominant disorder with an incidence of approximately one in 3500 persons; the remainder of MPNSTs develop sporadically. In addition to a variety of clinical manifestations, approximately 8–13% of NF1 patients develop MPNSTs, which are the leading cause of NF1-related mortality. Surgical resection is the mainstay of MPNST clinical management. However, because of invasive growth, propensity to metastasise, and limited sensitivity to chemotherapy and radiation, MPNST has a guarded to poor prognosis. Five-year survival rates of only 20–50% indicate an urgent need for improved therapeutic approaches. Recent work in this field has identified several altered intracellular signal transduction cascades and deregulated tyrosine kinase receptors, posing the possibility of personalised, targeted therapeutics. However, expanded knowledge of MPNST molecular pathobiology will be needed to meaningfully apply such approaches for the benefit of afflicted patients.
A Mechanism Related to the Yeast Transcriptional Regulator Paf1c Is Required for Expression of the Arabidopsis FLC/MAF MADS Box Gene Familyw⃞

The Arabidopsis thaliana VERNALIZATION INDEPENDENCE (VIP) gene class has multiple functions in development, including repression of flowering through activation of the MADSbox gene FLC. Epigenetic silencing of FLC plays a substantial role in the promotion of flowering through cold (vernalization). To better understand how VIP genes influence development, we undertook a genetic and molecular study of the previously uncharacterized VIP5 and VIP6 genes. We found that loss of function of these genes also resulted in downregulation of other members of the FLC/MAF gene family, including the photoperiodic pathway regulator MAF1/FLM. We cloned VIP5 and VIP6 through mapping and transcriptional profiling. Both proteins are closely related to distinct components of budding yeast Paf1C, a transcription factor that assists in establishment and maintenance of transcription-promotive chromatin modifications such as ubiquitination of H2B by Bre1/Rad6 and methylation of histone H3 lysine-4 by the trithorax-related histone methylase Set1. Genetic analysis and coimmunoprecipitation experiments suggest that VIP5 and VIP6 function in the same mechanism as the previously described VIP3 and VIP4. Our findings suggest that an evolutionarily conserved transcriptional mechanism plays an essential role in the maintenance of gene expression in higher eukaryotes and has a central function in flowering.
ATP Signaling in Skeletal Muscle: From Fiber Plasticity to Regulation of Metabolism

Tetanic electrical stimulation releases adenosine triphosphate (ATP) from muscle fibers through pannexin-1 channels in a frequency-dependent manner; extracellular ATP activates signals that ultimately regulate gene expression and is able to increase glucose transport through activation of P2Y receptors, phosphatidylinositol 3-kinase, Akt, and AS160. We hypothesize that this mechanism is an important link between exercise and the regulation of muscle fiber plasticity and metabolism.
Heterogeneously Catalyzed Phosphine-Free Heck Cross-Coupling Reaction of Aryl Halides with Reusable Palladium(II) Schiff Base Complex

The coupling between aryl halides with terminal alkenes (Heck reaction) has been investigated in the presence of a polystyrene-supported Schiff base palladium(II) catalyst. The present catalyst is air and moisture-stable and has significant catalytic activity in Heck cross-coupling reactions under operating conditions. Various aryl halides and terminal alkenes were coupled smoothly under air, to afford the corresponding cross-coupled products in excellent yields. Furthermore, the catalyst can be easily recovered quantitatively by simple filtration and reused up to seven cycles without losing its activity.
Methadone and l-methadyl acetate. Use in management of narcotics addicts.

Ten volunteer patients participating in a methadone hydrochloride maintenance program were assigned randomly to experimental (five patients) or control (five patients) groups. These patients had been in treatment for several months and had been stabilized (had no change of dose for at least three weeks) with methadone prior to inclusion in the study. Patients in the experimental group were given l-methadyl acetate (l-α acetylmethadol) on weekends and methadone on weekdays. Patients in the control group were given methadone each day. Clinic attendance, requests for change in medication, and scores on an opiate-withdrawal test instrument did not reveal differences between groups. Clinical observers blind to the experiment were unable to discriminate experimental and control patients. No untoward reactions were observed in either group. These preliminary observations suggest that l-methadyl acetate can be interchanged repeatedly with methadone without difficulty.
Opinion: When is Vitamin D Contraindicated in Dialysis Patients?

Fitzpatrick L, Goltzmann D, Lafage-Proust MH, Leonard M, Ott S, Rodriguez M, Stehman-Breen C, Stern P, Weisinger J: Osteoporosis in chronic kidney disease.AmJKidneyDis 43:566–571, 2004 24. Chertow GM, Raggi P, Chasan-Taber S, Bommer J, Holzer H, Burke SK: Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant 19:1489–1496, 2004 25. Block GA, Port FK: Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change inmanagement.AmJKidneyDis 35:1226–1237, 2000 26. HenleyC,CollotonM,CattleyRC, ShatzenE,TowlerDA,LaceyD,Martin D: 1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar ⁄Mimpara) treatment mediates aortic calcification in a rat model of secondary hyperparathyroidism.Nephrol Dial Transplant 20:1370–1377, 2005 27. O’Connell TD, Berry JE, Jarvis AK, Somerman MJ, Simpson RU: 1,25Dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and hypertrophy.AmJPhysiol 272:H1751–H1758, 1997 28. Raymond CB, Wazny LD: Sodium thiosulfate, bisphosphonates, and cinacalcet for treatment of calciphylaxis.Am JHealth Syst Pharm 65:1419–1429, 2008
Exercise induced myocardial ischaemia does not cause increase in C-reactive protein concentration

High plasma concentrations of C-reactive protein (CRP), which are predictive of a poor prognosis in patients with acute coronary syndromes,1 might reflect an inflammatory pathogenetic component. It is well known, however, that short periods of ischaemia are powerful inflammatory stimuli sufficient to induce the synthesis of acute phase reactants.2 Therefore, the acute phase response in acute coronary syndrome may simply reflect the extent and severity of myocardial ischaemia. To establish whether myocardial ischaemia is an adequate stimulus to induce an increase in CRP, its plasma concentrations were evaluated in a group of patients with chronic stable angina and normal baseline values of CRP in whom myocardial ischaemia was induced by exercise. Fifteen patients (10 men, mean (SD) age 60 (9) years) with chronic stable angina and reproducible positive exercise testing for myocardial ischaemia participated in this study. No patient had suffered a previous myocardial infarction and mean left ventricular ejection fraction was 62 (5)%. All patients had at least one critical stenosis in the proximal two thirds of one major epicardial coronary artery. The control group consisted of nine healthy subjects (six men, mean age 61 (9) years) without evidence of ischaemic heart disease and normal …
Recalculation of cardiovascular risk score as a surrogate marker of change in clinical care of diabetes patients: the Alphabet POEM project (Practice Of Evidence-based Medicine)

SUMMARY Aims: To assess the impact of evidence-based strategies on the care of subjects with diabetes, in particular on their coronary heart disease (CHD) risk, using the Alphabet Strategy template and coronary heart disease (CHD) risk calculators as novel audit tools. Methods: Diabetes and cardiovascular parameters were collected on 400 consecutive type 2 diabetes patients attending the outpatient clinic. The subjects were men and women aged 21-75 years with necessary follow-up data from referral or first chronological available letter in the notes (T0) to the most recent follow-up visit (Tfu). The average follow-up period was 5 years. Absolute CHD risk was calculated using the Framingham risk function and the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. The results were analysed using Student's paired t-test and chi-squared test. Results (T0 vs.Tfu): Advice: smoking status improved 18.3 vs. 15.5%: p = 0.3. Blood pressure: systolic blood pressure improved 145.8 ± 21.1 vs. 140.1 ± 20.5mmHg: p < 0.0001. Diastolic blood pressure improved 82.0 ± 12.2 vs. 76.5 ± 11.0mmHg: p < 0.0001. Cholesterol: total cholesterol improved 5.8 ± 1.6 vs. 4.9 ± 1.0 mmol/L: p < 0.0001; high density lipoprotein (HDL) cholesterol improved 1.05 vs. 1.26 mmol/L: p < 0.001. Diabetes control: glycated haemoglobin (HbA1c)% worsened 7.9 ± 1.8 vs. 8.1 ± 1.5: p < 0.0001. However, when adjusted for duration of diabetes, this improved non-significantly by 12% overall. Eye examination: improved 86.5 vs. 97.5%: p < 0.001. Feet examination: improved 69.8 vs. 83.5%: p < 0.001. Guardian drugs: significantly more patients were on aspirin (29.0 vs. 83.5%: p < 0.001), angiotensin converting enzyme (ACE) inhibitors (32.0 vs. 64.5%: p < 0.001), and lipid lowering therapy (16.8 vs. 55.0%: p < 0.001). Heart disease risk scores: a significant reduction in Framingham 10-year absolute cardiac risk was achieved (20.6 ± 10.04% vs. 16.7 ± 9.1%: p = 0.001). Using the UKPDS risk engine, there was a non-significant reduction in absolute CHD risk over the follow-up period (23.8 ± 14.8% vs. 23.7 ± 15.5: p = NS). There were significant improvements between age-adjusted risk score (Tadj) and follow-up values (Tfu) (Framingham: 23.67% (Tadj) vs. 16.7% (Tfu); UKPDS 31.2% (Tadj) vs. 23.7% (Tfu)). For UKPDS stroke risk, a significant improvement was seen from Tadj to Tfu (19.0% (Tadj) vs. 16.4% (Tfu): p < 0.001), with a significant deterioration noted between T0 and Tfu (11.5% (T0) vs. 16.4% (Tfu): p < 0.0001). Conclusions:The Alphabet Strategy is a novel evidence-based approach to clinical diabetes care, which produced a statistically significant improvement in most of the assessed parameters. The Alphabet Practice Of Evidence-based Medicine (POEM) template is a useful clinical tool for diabetes care and audit. It includes most of the components of diabetes audit required by the National Service Framework (NSF) and the United Kingdom GP contract.