Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Heterogeneity and Clonal Evolution of Tumor Cells and their Impact on Precision Cancer Medicine

The efficacy of targeted therapies in leukemias and solid tumors depends upon the accurate detection and sustained targeting of initial and evolving driver mutations and/or aberrations in cancer cells. Tumor clonal evolution of the diverse populations of cancer cells during cancer progression contributes to the longitudinal variations of clonal, morphological, anatomical, and molecular heterogeneity of tumors. Moreover, drug-resistant subclones present at initiation of therapy or emerging as a result of targeted therapies represent major challenges for achieving success of personalized therapies in providing meaningful improvement in cancer survival rates. Here, I briefly portray tumor cell clonal evolution at the cellular and molecular levels, and present the multiple types of genetic heterogeneity in tumors, with a focus on their impact on the implementation of personalized or precision cancer medicine.
A High-Efficiency Flyback Micro-inverter With a New Adaptive Snubber for Photovoltaic Applications

Based on the hybrid operation of interleaved flyback micro-inverter in discontinuous and boundary conduction modes (DCM and BCM), a novel adaptive snubber is proposed in this paper. The proposed snubber limits the drain-to-source voltage overshoot of the flyback's main switch during the turn-off process, enabling the use of lower voltage MOSFETs. It also recovers the stored energy in the leakage inductance of the flyback transformer and provides soft switching for the main flyback switch by limiting the rising slope of the MOSFET voltage during the turn-off process resulting in higher efficiency. Exploiting the natural resonant of the flyback converter in BCM, the adopted controller provides ZVS and ZCS for the main switch during the BCM operation. The operation of the flyback micro-inverter with associated controllers is analytically studied, and considerations for an optimum design aiming to higher efficiency are presented. Performance of the flyback micro-inverter with the proposed adaptive snubber and the corresponding controllers is experimentally verified based on a 250W interleaved flyback micro-inverter hardware setup.
Rough ISODATA Algorithm

Cluster analysis is a branch of data mining, which plays a vital role in bringing out hidden information in databases. Clustering algorithms help medical researchers in identifying the presence of natural subgroups in a data set. Different types of clustering algorithms are available in the literature. The most popular among them is k-means clustering. Even though k-means clustering is a popular clustering method widely used, its application requires the knowledge of the number of clusters present in the given data set. Several solutions are available in literature to overcome this limitation. The k-means clustering method creates a disjoint and exhaustive partition of the data set. However, in some situations one can come across objects that belong to more than one cluster. In this paper, a clustering algorithm capable of producing rough clusters automatically without requiring the user to give as input the number of clusters to be produced. The efficiency of the algorithm in detecting the number of clusters present in the data set has been studied with the help of some real life data sets. Further, a nonparametric statistical analysis on the results of the experimental study has been carried out in order to analyze the efficiency of the proposed algorithm in automatic detection of the number of clusters in the data set with the help of rough version of Davies-Bouldin index.
An Efficient Fungal RNA-Silencing System Using the DsRed Reporter Gene

ABSTRACT In filamentous fungi, RNA silencing is an attractive alternative to disruption experiments for the functional analysis of genes. We adapted the gene encoding the autofluorescent DsRed protein as a reporter to monitor the silencing process in fungal transformants. Using the cephalosporin C producer Acremonium chrysogenum, strains showing a high level of expression of the DsRed gene were constructed, resulting in red fungal colonies. Transfer of a hairpin-expressing vector carrying fragments of the DsRed gene allowed efficient silencing of DsRed expression. Monitoring of this process by Northern hybridization, real-time PCR quantification, and spectrofluorometric measurement of the DsRed protein confirmed that downregulation of gene expression can be observed at different expression levels. The usefulness of the DsRed silencing system was demonstrated by investigating cosilencing of DsRed together with pcbC, encoding the isopenicillin N synthase, an enzyme involved in cephalosporin C biosynthesis. Downregulation of pcbC can be detected easily by a bioassay measuring the antibiotic activity of individual strains. In addition, the presence of the isopenicillin N synthase was investigated by Western blot hybridization. All transformants having a colorless phenotype showed simultaneous downregulation of the pcbC gene, albeit at different levels. The RNA-silencing system presented here should be a powerful genetic tool for strain improvement and genome-wide analysis of this biotechnologically important filamentous fungus.
Thermally Modified Azocasein–A New Insoluble Substrate for the Determination of Proteolytic Activity

An insoluble chromogenic substrate for the determination of proteolytic activity was prepared by heating azocasein in a thin layer at 200 degrees C for 4 h in a hot‐air thermostat. The activity of an extracellular bacterial proteinase produced by Bacillus sp. was determined with this new substrate.
Self–other control processes in social cognition: from imitation to empathy

We review the evidence that an ability to achieve a precise balance between representing the self and representing other people is crucial in social interaction. This ability is required for imitation, perspective-taking, theory of mind and empathy; and disruption to this ability may contribute to the symptoms of clinical and sub-clinical conditions, including autism spectrum disorder and mirror-touch synaesthesia. Moving beyond correlational approaches, a recent intervention study demonstrated that training participants to control representations of the self and others improves their ability to control imitative behaviour, and to take another's visual perspective. However, it is unclear whether these effects apply to other areas of social interaction, such as the ability to empathize with others. We report original data showing that participants trained to increase self–other control in the motor domain demonstrated increased empathic corticospinal responses (Experiment 1) and self-reported empathy (Experiment 2), as well as an increased ability to control imitation. These results suggest that the ability to control self and other representations contributes to empathy as well as to other types of social interaction.
A penalty-BSUM approach for rate optimization in full-duplex MIMO relay networks with relay processing delay

This paper studies joint source transmit beamforming and relay amplification matrix design to achieve rate maximization for full-duplex (FD) MIMO amplify-and-forward (AF) relay systems with consideration of relay processing delay (RPD). The problem is difficult to solve due mainly to the self-interference constraint induced by the RPD. In this paper, we first propose a penalty-based algorithmic framework, called P-BSUM, for a class of constrained optimization problems with difficult equality constraints in addition to some convex constraints. We then apply the P-BSUM algorithm to the rate maximization problem and obtain a simple iterative algorithm. Finally, numerical results illustrate the efficiency of the proposed algorithm.
Estimated Glomerular Filtration Rate and Albuminuria as Predictors of Outcomes in Patients With High Cardiovascular Risk

BACKGROUND Glomerular filtration rate and albuminuria are risk factors for cardiovascular disease and markers of renal function. OBJECTIVE To examine the contribution of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio beyond that of traditional cardiovascular risk factors to classification of patient risk for cardiovascular and renal outcomes. DESIGN Prospective cohort study that pooled all patients of ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in Angiotensin-Converting-Enzyme-Inhibitor Intolerant Subjects with Cardiovascular Disease). PATIENTS 27,620 patients older than 55 years with documented cardiovascular disease, who were followed for a mean of 4.6 years. MEASUREMENTS Baseline eGFR, urinary albumin-creatinine ratio, and cardiovascular risk factors. Outcomes were all-cause mortality; a composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure; long-term dialysis; and a composite of long-term dialysis and doubling of serum creatinine level. RESULTS Lower eGFRs and higher urinary albumin-creatinine ratios were associated with the primary cardiovascular composite outcome (for example, an adjusted hazard ratio of 2.53 [95% CI, 1.61 to 3.99] for an eGFR <30 mL/min per 1.73 m(2) and a very high urinary albumin-creatinine ratio). However, adding information about eGFR and urinary albumin-creatinine ratio to the risk reclassification analyses led to no meaningful decrease in the proportion of patients assigned to the intermediate-risk category (31% without vs. 32% with renal information). In contrast, eGFR and urinary albumin-creatinine ratio were strongly associated with risk for long-term dialysis and greatly improved both model calibration and risk stratification capacity when added to traditional cardiovascular risk factors (65% assigned to intermediate-risk categories without renal information vs. 18% with renal information). LIMITATION Creatinine levels were not standardized. CONCLUSION In patients with high vascular risk, eGFR and urinary albumin-creatinine ratio add little to traditional cardiovascular risk factors for stratifying cardiovascular risk but greatly improve risk stratification for renal outcomes. PRIMARY FUNDING SOURCE Boehringer Ingelheim, Population Health Research Institute, and the European Commission.
Safety assessemt based on physically-viable data-driven models

We consider the problem of safety assessment of a dynamical system for which no model and just limited data on the states is available. That is, given samples of the state {x(t<inf>i</inf>)}<sup>N</sup><inf>i=1</inf> at time instances t<inf>1</inf> ≤ t<inf>2</inf> ≤ ••• ≤ t<inf>N</inf> and some other side information in terms of the regularity of the state evolutions, we are interested in checking whether x(T) ∉ Xu, where T > t<inf>N</inf> and Xu ⊂ R<sup>n</sup> (the unsafe set) are pre-specified. To this end, we use piecewise-polynomial approximations of the trajectories based on the data along with the regularity side information to formulate a data-driven differential inclusion model. For these classes of data-driven differential inclusions, we propose a safety assessment theorem based on barrier certificates. The barrier certificates are then found using polynomial optimization. The method is illustrated by two examples.
CD27‐triggering on primary plasma cell leukaemia cells has anti‐apoptotic effects involving mitogen activated protein kinases

Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was set out to assess the functional properties of CD27 expressed on PCL plasma cells by triggering with its ligand CD70. Using CD27‐expressing purified plasma cells from a PCL patient we demonstrated that CD27‐triggering modestly inhibited spontaneous and dexamethasone‐induced apoptosis. In vitro stimulation and Western blotting showed that activation of p38 and extracellular‐regulated kinase 1/2 (ERK1/2) mitogen‐activated protein kinases (MAPK) was associated with CD27‐mediated signal transduction. Specific inhibition of p38 and ERK1/2 MAPK abolished the anti‐apoptotic effects of CD27‐triggering. Interestingly, simultaneous inhibition of p38 and ERK1/2 strongly sensitized PCL cells for dexamethasone‐induced apoptosis. Finally, in dexamethasone‐treated PCL cells, CD27‐triggering was associated with persistent DNA‐binding activity of activator protein 1 (AP‐1) but not of nuclear factor‐κB. These findings suggest that, in primary PCL, specific anti‐apoptotic pathways exist that might provide novel therapeutic targets.
College Students' Attitudes, Perceived Consumer Effectiveness and Intention to Dine at a Green Restaurant

Many foodservice operators have accepted the importance of promoting environmental awareness to create competitive advantages. Despite this, limited research exists on consumers’ attitudes toward sustainable restaurant practices. Utilizing an adapted version of the Hines’ Model of Responsible Environmental Behavior, this study measured college students’ attitudes, perceived consumer effectiveness and their intention to dine at a green restaurant. Multivariate tests of significance revealed that each variable had a positive relationship on intention to dine at a green restaurant (p ≤ .001). Structural Equation Modeling revealed that the data adequately supported the hypothesized model with an R 2 of . 507.
Using Volunteers in Policing: A Force Field Analysis of American Supervisors

This study used a Force Field Analysis to assess the attitudes of American police supervisors regarding the use of volunteers in policing. Organisations exist in a state of quasi-stable equilibrium, and any planned change should work to identify the driving and restraining forces that function to maintain that equilibrium. For example, economic conditions may force police agencies to utilise volunteers to handle many policing tasks, but this may threaten the equilibrium of police organisations and traditional police culture. For this study a national sample of police supervisors completed a survey with attitude measures related to the use of volunteers in police work. Driving and restraining forces are identified and their strengths and weaknesses are discussed. Findings indicate that, with respect to the driving forces, the items associated with organising the community and community policing may be limited in their strength as driving forces. The power of the restraining forces indicates that the use of volunteers in policing is acceptable to this cohort of police supervisors. Aggressiveness in policing is a fairly strong restraining force. Bivariate correlation results indicate that supervisors with higher levels of education contribute to positive views of several volunteer aspects. Also, more experienced police supervisors do not feel volunteers are more trouble than they are worth. There appears to be a strong relationship between the need for volunteers as part of an agency's community policing philosophy, and volunteers are seen as important to reducing crime and disorder. Finally, several significant results suggest that volunteers are accepted within the police culture.
Bluetooth Network Re-formation protocol for reducing path length (BNR)

Bluetooth is a short range wireless communication technology. Bluetooth's basic units called a piconet which provides point-to-point and point-to-multipoint transmissions. Multiple piconets can connect at the same time to make a bigger ad hoc network called a scatternet. Therefore, different piconet transmissions can be achieved through multi-hop. An inefficient topology may create the longest route between a source and destination in a scatternet, which consumes extra resources. It is also observed that the pair of source and destination is in proximity of each other but cannot communicate directly or through the shortest path due to Bluetooth inherited properties. The objective of this paper is to solve the problem of the longest route for pairs of devices in a Bluetooth scatternet. The proposed Bluetooth Network Re-formation Protocol (BNR) reducespath length by performing network re-structuring that reduces the number of hop counts. Simulation results show that the proposed protocol reduces end-to-end delay and consumes less system resources.
Gene expression changes in HLA mismatched mixed lymphocyte cultures reveal genes associated with allorecognition

Abstract Human leucocyte antigen (HLA) compatibility is the main factor determining the occurrence of graft‐vs‐host disease (GVHD) in patients. It has also been shown that minor histocompatibility antigen differences as well as genetic polymorphisms that are not sequenced by standard methodology for HLA typing can play a role. We used mixed lymphocyte cultures (MLCs) as a functional cellular test and investigated gene expression changes driven by HLA incompatibility in an effort to better understand the mechanisms involved in the disease. Gene expression profile of HLA matched and HLA mismatched MLC identified differentially regulated genes and pathways. We found that a great number of genes related to immune function were differentially regulated; these genes were also found to be associated with GVHD and graft rejection. The majority of differentially regulated genes were interferon‐gamma (IFNγ)‐inducible genes and IFNγ neutralisation in MLCs abrogated their induction. The microRNA‐155, a recently identified target for acute GVHD (aGVHD), was also found to be significantly induced in HLA mismatched MLC but not in the matched setting and its induction was not diminished by blocking IFNγ. In this proof‐of‐principle study we show gene expression changes in mismatched MLC that represent alloreactive responses, correlate with markers involved in GVHD and can potentially be useful in the study of the biological processes involved in this disease.
Reliability and construct validity of the Clinical Observations of Motor and Postural Skills.

The Clinical Observations of Motor and Postural Skills (COMPS) is a screening tool for children with motor incoordination. A study of reliability (test-retest, interrater, and internal consistency) and construct validity with 132 children, both with and without developmental coordination disorder, is reported here. Test-retest reliability over 2 weeks was high: . 92 for a group of 48 children. Interrater reliability for occupational therapists experienced in pediatrics was also excellent: . 87 for a group of 72 children. Internal consistency of the COMPS was high, particularly when one of the seven items (Schilder's arm extension) was deleted. The test discriminates well between children with and without motor problems and has many properties of a good screening test.
General Mechanisms Underlying Language and Spatial Cognitive Development

Previous research showed that children’s spatial language production predicts their spatial skills, but the mechanisms underlying this relation remain a source of debate. This study examined whether 4-year-olds’ spatial skills were predicted by their attention to task-relevant information—in tasks that emphasize either memory or language—above and beyond their spatial word production. Children completed three types of tasks: (1) a memory task assessing attention to task-relevant color, size, and location cues; (2) a production task assessing adaptive use of language to describe scenes, varying in color, size, and location; and (3) spatial tasks. After controlling for age, gender, and vocabulary, children’s spatial skills were significantly predicted by their memory for task-relevant cues, above and beyond their task-related language production and adaptive use of language. These findings suggest that attending to relevant information is a process supporting spatial skill acquisition and underlies the relation between language and
Type-safe Runtime Code Generation with LLVM

Embedded languages are often compiled at application runtime; thus, embedded compile-time errors become application runtime errors. We argue that advanced type system features, such as GADTs and type families, play a crucial role in minimising such runtime errors. Specifically, a rigorous type discipline reduces runtime errors due to bugs in both embedded language applications and the implementation of the embedded language compiler itself. In this paper, we focus on the safety guarantees achieved by type preserving compilation. We discuss the compilation pipeline of Accelerate, a high-performance array language targeting both multicore CPUs and GPUs, where we are able to preserve types from the source language down to a low-level register language in SSA form. Specifically, we demonstrate the practicability of our approach by creating a new type-safe interface to the industrialstrength LLVM compiler infrastructure, which we used to build two new Accelerate backends that show competitive runtimes on a set of benchmarks across both CPUs and GPUs.
Quality of life in chronic lymphocytic leukemia: 5-year results from the multicenter randomized LRF CLL4 trial

Abstract Health-related quality of life (HRQoL) is a key issue for patients with chronic lymphocytic leukemia. The multicenter LRF CLL4 trial, in which 777 patients were randomized to receive chlorambucil or fludarabine, alone or with cyclophosphamide (FC), assessed HRQoL at baseline, months 3, 6 and 12, then annually until 5 years, using the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30). While on treatment, some HRQoL impairment was seen in patients receiving fludarabine, particularly FC, compared with chlorambucil. Thus at 3 months, role/social functioning and fatigue were ≥ 10 points worse than baseline in 41%/46%/56%, respectively, of patients receiving fludarabine alone and 48%/54%/60% receiving FC, compared with only 29%/31%/40% of those receiving chlorambucil. Thereafter HRQoL appeared similar between treatment groups. Sustained remissions were associated with long-term HRQoL benefit. In the primary HRQoL domains patients still in complete or partial remission at each time-point had scores close to those reported in general population studies, while patients whose disease had progressed had mean scores up to 22 points worse, in spite of subsequent treatments. These data offer support for the use of primary treatment regimens likely to achieve and sustain remission in otherwise medically fit patients of all ages, including those aged > 70 years.
In Vitro Synthesis of Peptidoglycan Precursors Modified with N-Acetylputrescine by Cyanophora paradoxa Cyanelle Envelope Membranes

ABSTRACT The photosynthetic organelles (cyanelles) of the protistCyanophora paradoxa are surrounded by a peptidoglycan wall, modified through amidation with N-acetylputrescine. Cyanelle envelope membrane preparations were shown to catalyze the lipid-linked steps of peptidoglycan biosynthesis as well as the putrescinylation and subsequent acetylation, occurring at the stage of lipid I and/or lipid II.