Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making

Background It is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported actionable results, are not well known. During the course of the current study, the Foundation One (F1) test generated data on a combination of somatic mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and deoxyribonucleic acid (DNA) copy number changes at ~250× coverage, while the Paradigm Cancer Diagnostic (PCDx) test generated the same type of data at >5,000× coverage, plus provided messenger RNA (mRNA) expression levels. We sought to compare and evaluate paired formalin-fixed paraffin-embedded tumor tissue using these two platforms. Methods Samples from patients with advanced solid tumors were submitted to both the F1 and PCDx vendors for NGS analysis. Turnaround time (TAT) was calculated. Biomarkers were considered clinically actionable if they had a published association with treatment response in humans and were assigned to the following categories: commercially available drug (CA), clinical trial drug (CT), or neither option (hereafter referred to as “None”). Results The demographics of the 21 unique patient tumor samples included ten men and eleven women, with a median age of 56 years. Due to insufficient archival tissue from the same collection period, in one case, we used samples from different collections. PCDx reported first results faster than F1 in 20 cases. When received at both vendors on the same day, PCDx reported first results for 14 of 15 cases, with a median TAT of 9 days earlier than F1 (P<0.0001). Categorization of CA compared to CT and none significantly favored PCDx (P=0.012). Conclusion In the current analysis, commercially available NGS platforms provided clinically relevant actionable targets (CA or CT) in 47%–67% of diverse cancer types. In the samples analyzed, PCDx significantly outperformed F1 in TAT, and had statistically significant higher clinically relevant actionable targets categorized as CA.
Toll-Like Receptor (TLR) 2 and TLR4 Differentially Regulate Doxorubicin Induced Cardiomyopathy in Mice

Recent evidence indicates that toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of dilated cardiomyopathy (DCM), but the exact mechanisms of their actions have not been elucidated. We explored the therapeutic potential of blocking TLRs in mice with established cardiomyopathy. Cardiomyopathy was generated by a single intraperitoneal injection of doxorubicin (10 mg/kg). Two weeks later, the mice were treated with TLR2 or TLR4 neutralizing antibody. Blocking TLR2, but not TLR4, activity not only reduced mortality, but also attenuated doxorubicin-induced cardiac dysfunction by 20% and inhibited myocardial fibrosis. To determine the differential effects of blocking TLR2 and TLR4 in chronic cardiomyopathy, mice were injected with doxorubicin (3.5 mg/kg) once a week for 8 weeks, followed by treatment with TLR2 or TLR4 neutralizing antibody for 40 days. Blocking TLR2 activity blunted cardiac dysfunction by 13% and inhibited cardiac fibrosis, which was associated with a significant suppression of myocardial inflammation. The underlying mechanism involved interrupting the interaction of TLR2 with its endogenous ligands, resulting in attenuation of inflammation and fibrosis. In contrast, blocking TLR4 exacerbated cardiac dysfunction and fibrosis by amplifying inflammation and suppressing autophagy. Our studies demonstrate that TLR2 and TLR4 play distinct roles in the progression of doxorubicin-induced DCM. TLR4 activity is crucial for the resolution of inflammation and cardiac fibrosis, while blocking TLR2 activity has therapeutic potential for the treatment of DCM.
BCC: Reducing False Aborts in Optimistic Concurrency Control with Low Cost for In-Memory Databases

The Optimistic Concurrency Control (OCC) method has been commonly used for in-memory databases to ensure transaction serializability --- a transaction will be aborted if its read set has been changed during execution. This simple criterion to abort transactions causes a large proportion of false positives, leading to excessive transaction aborts. Transactions aborted false-positively (i.e. false aborts) waste system resources and can significantly degrade system throughput (as much as 3.68x based on our experiments) when data contention is intensive. Modern in-memory databases run on systems with increasingly parallel hardware and handle workloads with growing concurrency. They must efficiently deal with data contention in the presence of greater concurrency by minimizing false aborts. This paper presents a new concurrency control method named Balanced Concurrency Control (BCC) which aborts transactions more carefully than OCC does. BCC detects data dependency patterns which can more reliably indicate unserializable transactions than the criterion used in OCC. The paper studies the design options and implementation techniques that can effectively detect data contention by identifying dependency patterns with low overhead. To test the performance of BCC, we have implemented it in Silo and compared its performance against that of the vanilla Silo system with OCC and two-phase locking (2PL). Our extensive experiments with TPC-W-like, TPC-C-like and YCSB workloads demonstrate that when data contention is intensive, BCC can increase transaction throughput by more than 3x versus OCC and more than 2x versus 2PL; meanwhile, BCC has comparable performance with OCC for workloads with low data contention.
Vps15p regulates the distribution of cup‐shaped organelles containing the major eisosome protein Pil1p to the extracellular fraction required for endocytosis of extracellular vesicles carrying metabolic enzymes

Exosomes are small vesicles secreted from virtually every cell from bacteria to humans. Saccharomyces cerevisiae is a model system to study trafficking of small vesicles in response to changes in the environment. When yeast cells are grown in low glucose, vesicles carrying gluconeogenic enzymes are present as free vesicles and aggregated clusters in the cytoplasm. These vesicles are also secreted into the periplasm and account for more than 90% of total extracellular organelles, while less than 10% are larger 100–300 nm structures with unknown functions. When glucose is added to glucose‐starved cells, secreted vesicles are endocytosed and then targeted to the vacuole. Recent secretomic studies indicated that more than 300 proteins involved in diverse biological functions are secreted during glucose starvation and endocytosed during glucose re‐feeding. We hypothesised that extracellular vesicles are internalised using novel mechanisms independent of clathrin‐mediated endocytosis.
LIGNINOLYTIC ACTIVITY PATTERNS OF Pleurotus ostreatus OBTAINED BY SUBMERGED FERMENTATION IN PRESENCE OF 2,6-DIMETHOXYPHENOL AND REMAZOL BRILLIANT BLUE R DYE

The degradation of 2,6-dimethoxyphenol (DMP) and decolorization of Remazol brilliant blue R dye (RBB), added to culture media of Pleurotus ostreatus developed in submerged fermentation, and the laccase, manganese peroxidase and veratryl alcohol oxidase activities produced in these systems were evaluated. Both compounds were removed from the culture medium mainly by enzymatic action. These compounds decreased the specific growth rate and the effect on the maximal biomass values was not important. The enzymatic activities were increased by DMP and/or RBB; however, the DMP showed a higher inducer effect on all enzymes than RBB. On the other hand, the RBB showed a larger inducer effect on manganese peroxidase activity than on the laccases and veratryl alcohol oxidase activities. These results show that DMP was a better inducer of ligninolytic enzymes than dye, and the process of dye decolorization and degradation of DMP requires the action of all enzymes of the ligninolytic complex.
Constraint-induced movement therapy in patients with stroke: a pilot study on effects of small group training and of extended mitt use

Objective: (1) To evaluate constraint-induced movement therapy for chronic stroke patients modified into group practice to limit the demand on therapist resources. (2) To explore whether extended mitt use alone may enhance outcome. Design: A combined case-control and randomized controlled study with pre- and post-treatment measures by blinded observers. Setting: A university hospital rehabilitation department. Participants: Sixteen stroke patients (nine men and seven women; mean age 56.7 years; on average 28.9 months post stroke, five of whom were 6-9 months post stroke) with moderate motor impairments in the contralateral upper limb. Intervention: Constraint-induced therapy (mitt on the less affected hand 90% of waking hours for 12 days) with 2-3 patients per therapist and 6 h of group training per day. After the training period, the patients were randomized either to using the mitt at home every other day for two-week periods for another three months (in total 21 days) or to no further treatment. Outcome measures: Modified Motor Assessment Scale, Sollerman Hand Function Test, Two-Point Discrimination test and Motor Activity Log. Results: The mean motor performance improved significantly after two weeks of constraint-induced group therapy on Motor Assessment Scale (1.44 (95% confidence interval (95% CI) 0.59-2.28) points; P = 0.003) and on Sollerman Hand Function Test (3.81 (95% CI 0.26-7.36) points; P = 0.037) but showed no sensory change in the Two-Point Discrimination Test (P = 0.283). The median difference in self-reported motor ability (Motor Activity Log) also improved (P B=0.001). However, no additional effect was seen from wearing a mitt for another three months. Conclusion: Constraint-induced group therapy, allowing several patients per therapist, seems to be a feasible alternative to improve upper limb motor function. The restraint alone, extended in time, did not enhance the treatment effect.
Decreased Frequencies of Circulating CD4+ T Follicular Helper Cells Associated with Diminished Plasma IL-21 in Active Pulmonary Tuberculosis

Background Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored. Aims/Methodology To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS. Results We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro. Conclusions Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.
Do students differentiate between computing disciplines?

We are in a time where computing programs are seeking to differentiate themselves. The ACM suggests that there are five distinct computing disciplines -- Computer Science (CS), Information Technology (IT), Information Systems (IS), Computer Engineering (CE), and Software Engineering (SE). In practice, it seems that there can be extensive overlap between these disciplines. For example, IS is defined by the ACM as computing in an organization context, typically in business while IT is defined as focusing on computing infrastructure and needs of individual users. If each of the different types of programs wishes to identify and attract interested students, it is important to understand if students perceive differences between them. This paper presents the results of a survey to determine if students differentiate between these five disciplines. Computing majors and non-majors were presented with several task descriptions commonly associated with each discipline and asked to identify them as belonging to one of the five disciplines. Data was collected from over 300 students at several different institutions and from a variety of different majors and computing disciplines. The results of the survey are presented along with comparisons of the perceptions of majors and non-majors.
A Whole Page Click Model to Better Interpret Search Engine Click Data

Recent advances in click modeling have established it as an attractive approach to interpret search click data. These advances characterize users’ search behavior either in advertisement blocks, or within an organic search block through probabilistic models. Yet, when searching for information on a search result page, one is often interacting with the search engine via an entire page instead of a single block. Consequently, previous works that exclusively modeled user behavior in a single block may sacrifice much useful user behavior information embedded in other blocks. To solve this problem, in this paper, we put forward a novel Whole Page Click (WPC) Model to characterize user behavior in multiple blocks. Specifically, WPC uses a Markov chain to learn the user transition probabilities among different blocks in the whole page. To compare our model with the best alternatives in the Web-Search literature, we run a large-scale experiment on a real dataset and demonstrate the advantage of the WPC model in terms of both the whole page and each block in the page. Especially, we find that WPC can achieve significant gain in interpreting the advertisement data, despite of the sparsity of the advertisement click data.
Some Designs and Normalized Diversity Product Upper Bounds for Lattice-Based Diagonal and Full-Rate Space–Time Block Codes

In this paper, we first present two tight upper bounds for the normalized diversity products (or product distances) of <i>2&nbsp;&times;&nbsp;2</i> diagonal space-time block codes from quadratic extensions on <i>\BBQ (</i>i<i>) </i> and <i> \BBQ ( \mmbzeta<sub>6</sub>)</i>, where i <i>=radic{-1}</i> and <i>\mmbzeta<sub>6</sub>=exp( </i>i<i> 2pi/6)</i>. Two such codes are shown to reach the tight upper bounds and therefore have the maximal normalized diversity products. We present two new diagonal space-time block codes from higher order algebraic extensions on <i>\BBQ (</i>i<i>) </i> and <i> \BBQ ( \mmbzeta<sub>6</sub>)</i> for three and four transmit antennas. We also present a nontight upper bound for normalized diversity products of <i>2&nbsp;&times;&nbsp;2</i> diagonal space-time block codes with QAM information symbols, i.e., in <i>\BBZ [</i>i<i> ]</i>, from general <i>2&nbsp;&times;&nbsp;2 </i> complex-valued generating matrices. We then present an <i><i>n</i>&nbsp;&times;&nbsp;<i>n</i></i>-diagonal space-time code design method directly from <i> 2<i>n</i></i> real integers based on extended complex lattices (of generating matrix size <i><i>n</i>&nbsp;&times;&nbsp;2<i>n</i></i>) that are shown to have better normalized diversity products than the optimal diagonal cyclotomic codes do. We finally use the optimal <i>2&nbsp;&times;&nbsp;2</i> diagonal space-time codes from the optimal quadratic extensions to construct two <i>2&nbsp;&times;&nbsp;2 </i> full-rate space-time block codes and find that both of them have better normalized diversity products than the Golden code does.
Thermohaline and Hydrocarbon Related Diagenesis of Lower Miocene and Upper Oligocene Sediments, West Hackberry Field, Cameron Parish, Louisiana: Implications for Mass Transport and Fluid Flow.

The diagenesis of Lower Miocene and Upper Oligocene sediments flanking the West Hackberry salt dome are documented in order to determine the effect the presence of salt domes may have in driving diagenetic reactions in detrital siliciclastic sediments. These sediments have undergone significant chemical diagenesis during progressive burial resulting in a reduction in porosity and permeability. Precipitation of analcime, siderite, and calcite plus the alteration of detrital volcanic lithic fragments and replacement of aluminosilicate framework grains by calcite are the dominant reactions which have altered the Upper Oligocene sands. Analcime and siderite are also present in the Oligocene mudstones. The isotopic composition of the Oligocene calcites is quite variable suggesting multiple generations of calcite cement, an early one precipitated from seawater and perhaps several later ones precipitated during progressive burial by warm, hydrocarbon enriched, diagenetic pore fluids similar in composition to present day brines. Petrographic evidence suggests an extraformational source is required to account for the occurrence of these authigenic minerals. The most likely sources include the dissolution of halite in the adjacent salt dome, the dissolution and alteration of volcanic lithic fragments and aluminosilicates, and the smectite to illite transformation in more deeply buried sediments. The dominant reactions affecting the composition, porosity, and permeability of the Lower Miocene sands are precipitation of calcite and iron sulfides and replacement of detrital framework grains. Iron sulfide nodules of complex mineralogy and paragenesis occur in interbedded mudstones. The isotopic composition of the calcite is relatively constant and is consistent with the hypothesis that dissolution of Jurassic anhydrite in the adjacent salt dome and oxidation of methane are the primary sources for Ca and
Bioactive thermoresponsive hydrogels for neural tissue engineering

Traumatic injury to the central nervous system triggers cell death and deafferentation, which may activate a cascade of cellular and network disturbances. These events often result in the formation of irregularly shaped lesions comprised of necrotic tissue and/or a fluid-filled cavity. Tissue engineering represents a promising treatment strategy for the injured neural tissue. To facilitate minimally invasive delivery of a tissue engineered system, a thermoreversible polymer is an attractive scaffold candidate. We have developed a bioactive scaffold for neural tissue engineering by tethering laminin-1 (LN) to methylcellulose (MC), a thermoresponsive hydrogel. The base MC chain was oxidized via sodium m-periodate to increase MC tethering capacity. Protein immobilization was facilitated by a Schiff base reaction between primary amine groups on LN and the carbonyl groups of the oxidized MC chain. Immunoassays demonstrated tethering of LN at 1.6 ± 0.5 ng of LN per mg of MC. Rheological measurements for different MC-LN constructs indicated MC compositionand MC treatment-dependent effects on solution-gelation transition temperature. Cellular assays with primary rat cortical neurons demonstrated enhanced cell adhesion and viability on LN-functionalized MC compared to base and oxidized MC. This bioadhesive
Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration

Q344ter is a naturally occurring rhodopsin mutation in humans that causes autosomal dominant retinal degeneration through mechanisms that are not fully understood, but are thought to involve an early termination that removed the trafficking signal, QVAPA, leading to its mislocalization in the rod photoreceptor cell. To better understand the disease mechanism(s), transgenic mice that express Q344ter were generated and crossed with rhodopsin knockout mice. Dark-reared Q344terrho+/− mice exhibited retinal degeneration, demonstrating that rhodopsin mislocalization caused photoreceptor cell death. This degeneration is exacerbated by light-exposure and is correlated with the activation of transducin as well as other G-protein signaling pathways. We observed numerous sub-micrometer sized vesicles in the inter-photoreceptor space of Q344terrho+/− and Q344terrho−/− retinas, similar to that seen in another rhodopsin mutant, P347S. Whereas light microscopy failed to reveal outer segment structures in Q344terrho−/− rods, shortened and disorganized rod outer segment structures were visible using electron microscopy. Thus, some Q344ter molecules trafficked to the outer segment and formed disc structures, albeit inefficiently, in the absence of full length wildtype rhodopsin. These findings helped to establish the in vivo role of the QVAPA domain as well as the pathways leading to Q344ter-induced retinal degeneration.
Position Paper: Whole Bowel Irrigation

Whole bowel irrigation (WBI) should not be used routinely in the management of the poisoned patient. Although some volunteer studies have shown substantial decreases in the bioavailability of ingested drugs, no controlled clinical trials have been performed and there is no conclusive evidence that WBI improves the outcome of the poisoned patient. Based on volunteer studies, WBI should be considered for potentially toxic ingestions of sustained‐release or enteric‐coated drugs particularly for those patients presenting greater than two hours after drug ingestion. WBI should be considered for patients who have ingested substantial amounts of iron as the morbidity is high and there is a lack of other options for gastrointestinal decontamination. The use of WBI for the removal of ingested packets of illicit drugs is also a potential indication. WBI is contraindicated in patients with bowel obstruction, perforation, ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients or in patients with medical conditions that may be further compromised by its use. The concurrent administration of activated charcoal and WBI may decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. A review of the literature since the preparation of the 1997 Whole Bowel Irrigation Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.
Dissecting the contribution of microtubule behaviour in adventitious root induction

Induction of adventitious roots (ARs) in recalcitrant plants often culminates in cell division and callus formation rather than root differentiation. Evidence is provided here to suggest that microtubules (MTs) play a role in the shift from cell division to cell differentiation during AR induction. First, it was found that fewer ARs form in the temperature-sensitive mutant mor1-1, in which the MT-associated protein MOR1 is mutated, and in bot1-1, in which the MT-severing protein katanin is mutated. In the two latter mutants, MT dynamics and form are perturbed. By contrast, the number of ARs increased in RIC1-OX3 plants, in which MT bundling is enhanced and katanin is activated. In addition, any1 plants in which cell walls are perturbed made more ARs than wild-type plants. MT perturbations during AR induction in mor1-1 or in wild-type hypocotyls treated with oryzalin led to the formation of amorphous clusters of cells reminiscent of callus. In these cells a specific pattern of polarized light retardation by the cell walls was lost. PIN1 polarization and auxin maxima were hampered and differentiation of the epidermis was inhibited. It is concluded that a fine-tuned crosstalk between MTs, cell walls, and auxin transport is required for proper AR induction.