Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Human Cyclin-Dependent Kinase 12 (CDK12) and CDK13 Complexes in C-Terminal Domain Phosphorylation, Gene Transcription, and RNA Processing

ABSTRACT Cyclin-dependent kinase 9 (CDK9) and CDK12 have each been demonstrated to phosphorylate the RNA polymerase II C-terminal domain (CTD) at serine 2 of the heptad repeat, both in vitro and in vivo. CDK9, as part of P-TEFb and the super elongation complex (SEC), is by far the best characterized of CDK9, CDK12, and CDK13. We employed both in vitro and in vivo assays to further investigate the molecular properties of CDK12 and its paralog CDK13. We isolated Flag-tagged CDK12 and CDK13 and found that they associate with numerous RNA processing factors. Although knockdown of CDK12, CDK13, or their cyclin partner CCNK did not affect the bulk CTD phosphorylation levels in HCT116 cells, transcriptome sequencing (RNA-seq) analysis revealed that CDK12 and CDK13 losses in HCT116 cells preferentially affect expression of DNA damage response and snoRNA genes, respectively. CDK12 and CDK13 depletion also leads to a loss of expression of RNA processing factors and to defects in RNA processing. These findings suggest that in addition to implementing CTD phosphorylation, CDK12 and CDK13 may affect RNA processing through direct physical interactions with RNA processing factors and by regulating their expression.
Vancomycin-resistant Enterococcal Bacteremia in a Hematology Unit: Molecular Epidemiology and Analysis of Clinical Course

An increase in vancomycin-resistant enterococcal (VRE) bacteremia in hemato-oncological patients (n=19) in our institution from 2000 through 2001 led us to analyze the molecular epidemiologic patterns and clinical features unique to our cases. The pulsed field gel electrophoresis of the isolates revealed that the bacteremia was not originated from a single clone but rather showed endemic pattern of diverse clones with small clusters. A different DNA pattern of blood and stool isolates from one patient suggested exogenous rather than endogenous route of infection. Enterococcus faecium carrying vanA gene was the causative pathogen in all cases. Patients with VRE bacteremia showed similar clinical courses compared with those with vancomycin-susceptible enterococcal (VSE) bacteremia. Vancomycin resistance did not seem to be a poor prognostic factor because of similar mortality (5/8, 62.5%) noted in VSE bacteremia. Initial disease severity and neutropenic status may be major determinants of prognosis in patients with VRE bacteraemia.
A single EGF‐like motif of laminin is responsible for high affinity nidogen binding.

A major nidogen binding site of mouse laminin was previously localized to about three EGF‐like repeats (Nos 3–5) of its B2 chain domain III [M. Gerl et al. (1991) Eur. J. Biochem. , 202, 167]. The corresponding cDNA was amplified by polymerase chain reaction and inserted into a eukaryotic expression vector tagged with a signal peptide. Stably transfected human kidney cell clones were shown to process and secrete the resulting fragment B2III3‐5 in substantial quantities. It possessed high binding activity for recombinant nidogen in ligand assays, with an affinity comparable with that of authentic laminin fragments. In addition, complexes of B2III3‐5 and nidogen could be efficiently converted into a covalent complex by cross‐linking reagents. Proteolytic degradation of the covalent complex demonstrated the association of B2III3‐5 with a approximately 80 residue segment of nidogen domain G3 to which laminin binding has previously been attributed. The correct formation of most of the 12 disulfide bridges in B2III3‐5 was indicated from its protease resistance and the complete loss of cross‐reacting epitopes as well as of nidogen‐binding activity after reduction and alkylation. Smaller fragments were prepared by the same recombinant procedure and showed that combinations of EGF‐like repeats 3–4 and 4–5 and the single repeat 4 but not repeats 3 or 5 possess full nidogen‐binding activity. This identifies repeat 4 as the only binding structure. The sequence of repeat 4 is well conserved in the human and in part in the Drosophila laminin B2 chain. (ABSTRACT TRUNCATED AT 250 WORDS)
An Interferometric Search for Bright Companions to 51 Pegasi

We report on a near-infrared, long-baseline interferometric search for luminous companions to the star 51 Pegasi conducted with the Palomar Testbed Interferometer. Our data is completely consistent with a single-star hypothesis. We find no evidence to suggest a luminous companion to 51 Pegasi, and we can exclude a companion brighter than a ΔK of 4.27 at the 99% confidence level for the 4.2 day orbital period indicated by spectroscopic measurements. This ΔK corresponds to an upper limit in the companion MK of 7.30, which in turn implies a main-sequence companion mass of less than 0.22 M☉.
Biologic and immunomodulatory events after CTLA‐4 blockade with ticilimumab in patients with advanced malignant melanoma

T‐regulatory (TR) cells expressing cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) maintain peripheral immune tolerance and negatively affect host immune responses against cancer. The immunobiologic effects of ticilimumab, a human monoclonal antibody against CTLA‐4, was administered to patients with metastatic melanoma who participated in a Phase I/II clinical trial.
Integrated Powertrain Control of Gearshift for Automatic Transmission

In this paper, an integrated powertrain control of gearshift for automatic transmission is developed: engine control by torque regulation is incorporated to suppress the shock of output shaft torque, whilst a clutch slip controller is applied to transfer the engine torque to driveline system, which is aimed to regulate clutch slip speed. The proposed approach ensure the powertrain system stable, and the shift time can be controlled by clutch slip controller even if with the absence of engine control. At last, taking 1-2 upshift for example, simulation results are presented and discussed in the final chapter of this paper.
Improving Handwritten Chinese Text Recognition by Unsupervised Language Model Adaptation

This paper investigates the effects of unsupervised language model adaptation (LMA) in handwritten Chinese text recognition. For no prior information of recognition text is available, we use a two-pass recognition strategy. In the first pass, the generic language model (LM) is used to get a preliminary result, which is used to choose the best matched LMs from a set of pre-defined domains, then the matched LMs are used in the second pass recognition. Each LM is compressed to a moderate size via the entropy-based pruning, tree-structure formatting and fewer-byte quantization. We evaluated the LMA for five LM types, including both character-level and word-level ones. Experiments on the CASIA-HWDB database show that language model adaptation improves the performance for each LM type in all domains. The documents of ancient domain gained the biggest improvement of character-level correct rate of 5.87 percent up and accurate rate of 6.05 percent up.
Spargel/dPGC-1 Is a New Downstream Effector in the Insulin–TOR Signaling Pathway in Drosophila

Insulin and target of rapamycin (TOR) signaling pathways converge to maintain growth so a proportionate body form is attained. Insufficiency in either insulin or TOR results in developmental growth defects due to low ATP level. Spargel is the Drosophila homolog of PGC-1, which is an omnipotent transcriptional coactivator in mammals. Like its mammalian counterpart, Spargel/dPGC-1 is recognized for its role in energy metabolism through mitochondrial biogenesis. An earlier study demonstrated that Spargel/dPGC-1 is involved in the insulin–TOR signaling, but a comprehensive analysis is needed to understand exactly which step of this pathway Spargel/PGC-1 is essential. Using genetic epistasis analysis, we demonstrated that a Spargel gain of function can overcome the TOR and S6K mediated cell size and cell growth defects in a cell autonomous manner. Moreover, the tissue-restricted phenotypes of TOR and S6k mutants are rescued by Spargel overexpression. We have further elucidated that Spargel gain of function sets back the mitochondrial numbers in growth-limited TOR mutant cell clones, which suggests a possible mechanism for Spargel action on cells and tissue to attain normal size. Finally, excess Spargel can ameliorate the negative effect of FoxO overexpression only to a limited extent, which suggests that Spargel does not share all of the FoxO functions and consequently cannot significantly rescue the FoxO phenotypes. Together, our observation established that Spargel/dPGC-1 is indeed a terminal effector in the insulin–TOR pathway operating below TOR, S6K, Tsc, and FoxO. This led us to conclude that Spargel should be incorporated as a new member of this growth-signaling pathway.
Pulse Pressure and Effects of Losartan or Atenolol in Patients With Hypertension and Left Ventricular Hypertrophy

In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the primary composite end point of cardiovascular death, stroke, and myocardial infarction was reduced by losartan versus atenolol in patients with hypertension and left ventricular hypertrophy. The objective of this post hoc analysis was to determine the influence of pulse pressure on outcome. Patients were divided into quartiles of baseline pulse pressure. Cox regression, including baseline Framingham risk score as a covariate, was used to compare risk in the quartiles. In the atenolol group, there were significantly higher risks in the highest versus lowest quartile for the composite end point 28% (confidence interval [CI], 2% to 62%; P=0.035), stroke 84% (CI, 32% to 157%; P<0.001), and total mortality 41% (CI, 7% to 84%; P=0.013). Risk for myocardial infarction was 44% higher (CI, −5% to 120%; P=0.089). The risks in the losartan group also increased with increasing quartile, but were lower than in the atenolol group, and differences between the highest and lowest quartiles were not significant: composite end point 12% (CI, −13% to 44%; P>0.2), stroke −5% (CI, −34% to 37%; P>0.2), myocardial infarction 30% (CI, −13% to 94%; P>0.2), and total mortality 32% (CI, −1% to 76%; P=0.062). In patients with hypertension and left ventricular hypertrophy in the LIFE study, there were significantly higher risks, adjusted for the Framingham risk score, for the primary composite end point, stroke, and total mortality in the highest versus lowest quartile of pulse pressure with atenolol-based treatment. The risks in the losartan group also increased with increasing pulse pressure quartile, but were lower than those in the atenolol group, and were not significant.
ECLIPSE: Error Correction based on Loss probability and data Importance for Plural Server Environment

Video streaming technique is widely used in the Internet with the development of access networks. Although some techniques such as Forward Error Correction or Content Distribution Network are effective for video streaming services, they are not sufficient in the case that streams are suffered from heavy packet loss. For this problem, we propose a novel error correction method called “ECLIPSE: Error Correction based on Loss probability and data Importance for Plural Server Environment”. The ECLIPSE recovers lost packets with a parity stream which exploits multiple streams. In order to improve video quality, ECLIPSE gives priority to each data of multiple streams in terms of recovery from packet losses. It is designed for recovering important data with higher probability. The priority of each data is set based on two criteria. The one is the inherent importance of the data within one stream. The other is the loss probability of one stream which is compared with the loss probabilities of other streams. We also clarify the performance of the proposed method through theoretical analysis. Moreover, we focus on the creation method of redundant data. They are transferred from another server for multiple worse conditioned streams, which greatly affects the recovery capability. We propose the adaptive creation method for various network conditions. Our simulation results show that the ECLIPSE can recover more important data with higher probability. Furthermore, it can also achieve almost the same restoration ratio among streams of recovery targets which have different loss probabilities.
Automated Feature Generation in Large-Scale Geospatial Libraries for Content-Based Indexing.

We describe a method for indexing and retrieving high-resolution image regions in large geospatial data libraries. An automated feature extraction method is used that generates a unique and specific structural description of each segment of a tessellated input image file. These tessellated regions are then merged into similar groups, or sub-regions, and indexed to provide flexible and varied retrieval in a query-by-example environment. The methods of tessellation, feature extraction, sub-region clustering, indexing, and retrieval are described and demonstrated using a geospatial library representing a 153 km2 region of land in East Tennessee at 0.5 m per pixel resolution.
Machine Transliteration

It is challenging to translate names and technical terms across languages with different alphabets and sound inventories. These items are commonly transliterated, i.e., replaced with approximate phonetic equivalents. For example, computer in English comes out as (konpyuutaa) in Japanese. Translating such items from Japanese back to English is even more challenging, and of practical interest, as transliterated items make up the bulk of text phrases not found in bilingual dictionaries. We describe and evaluate a method for performing backwards transliterations by machine. This method uses a generative model, incorporating several distinct stages in the transliteration process.
Study of Heavy Metal Air Pollution, Using a Moss (Grimmia dissimulate) Biomonitoring Technique

Air pollution is a problem in both developed and developing countries. As a corrective measure, constant air monitoring is usually performed by conventional techniques which are costly and time consuming hence the need for cheaper methods. Recently, biomonitoring has emerged as an effective alternative method. The aim of this study was to investigate heavy metal air pollution in the environment using Mosses. Mosses are lower plants that can provide a surrogate and time-integrated means of measuring elemental depositions from the atmosphere to terrestrial systems. Atmospheric deposition of heavy metals Chromium (Cr), Copper (Cu), lead (Pb), and Zinc (Zn) was studied at the University of Zimbabwe. Moss samples were hung on sites selected by a systematic grid sampling method, during the summer of 2016. The concentrations of heavy metals were determined by Atomic Absorption Spectroscopy (AAS). The concentrations were expressed as Relative Accumulation Factors (RAFs) and the means for Cr, Cu, Pb and Zn were 14.38; 18.17; 9.63 and 10.78 respectively. The results showed the concentration order of deposition was Cu > Cr > Zn >Pb and that Zn deposited uniformly as evidenced by its low sample variance which was more than 17 and 56 times smaller than that of Pb and Cr-Cu respectively. Although the distribution patterns of Cr and Cu were similar, Pb and Zn had their own patterns. The results suggested that the source of heavy metal could be from traffic related air pollutants.
Transport in networks with multiple sources and sinks

We investigate the electrical current and flow (number of parallel paths) between two sets of n sources and n sinks in complex networks. We derive analytical formulas for the average current and flow as a function of n. We show that for small n, increasing n improves the total transport in the network, while for large n bottlenecks begin to form. For the case of flow, this leads to an optimal n* above which the transport is less efficient. For current, the typical decrease in the length of the connecting paths for large n compensates for the effect of the bottlenecks. We also derive an expression for the average flow as a function of n under the common limitation that transport takes place between specific pairs of sources and sinks.
Accelerating neuro-evolution by compilation to native machine code

Any neuro-evolutionary algorithm that solves complex problems needs to deal with the issue of computational complexity. We show how a neural network (feed-forward, recurrent or RBF) can be transformed and then compiled in order to achieve fast execution speeds without requiring dedicated hardware like FPGAs. The compiled network uses a simple external data structure—a vector—for its parameters. This allows the weights of the neural network to be optimised by the evolutionary process without the need to re-compile the structure. In an experimental comparison our method effects a speedup of factor 5–10 compared to the standard method of evaluation (i.e., traversing a data structure with optimised C++ code)
Increased Turnover of Dopamine in Caudate Nucleus of Detoxified Alcoholic Patients

A previous study of the DOPA decarboxylase substrate 6-[18F]fluoro-L-DOPA (FDOPA) with positron emission tomography (PET) detected no difference of the net blood-brain transfer rate (Kinapp) between detoxified alcoholic patients and healthy controls. Instead, the study revealed an inverse correlation between Kinapp in left ventral striatum and alcohol craving scores. To resolve the influx and efflux phases of radiolabeled molecules, we independently estimated the unidirectional blood-brain FDOPA clearance rate (K) and the washout rate of [18F]fluorodopamine and its deaminated metabolites (k loss), and we also calculated the total distribution volume of decarboxylated metabolites and unmetabolized FDOPA as a steady-state index of the dopamine storage capacity (Vd) in brain. The craving scores in the 12 alcoholics correlated positively with the rate of loss (kloss) in the left ventral striatum. We conclude that craving is most pronounced in the individuals with relatively rapid dopamine turnover in the left ventral striatum. The blood-brain clearance rate (K), corrected for subsequent loss of radiolabeled molecules from brain, was completely normal throughout the brain of the alcoholics, in whom the volume of distribution (Vd) was found to be significantly lower in the left caudate nucleus. The magnitude of Vd in the left caudate head was reduced by 43% relative to the 16 controls, consistent with a 58% increase of kloss. We interpret the findings as indicating that a trait for rapid dopamine turnover in the ventral striatum subserves craving and reward-dependence, leading to an acquired state of increased dopamine turnover in the dorsal striatum of detoxified alcoholic patients.
A biologic role of HIF-1 in the renal medulla.

BACKGROUND Activation of hypoxia-inducible factor-1 (HIF-1) is the primary defensive mechanism against hypoxia. HIF-1 activation generally occurs in pathologic disruption of tissue oxygenation. However, a biologic role of HIF-1 in the medulla of the kidney, which is considered perpetually hypoxic under physiologic conditions due to its unique circulation, remains to be elucidated. METHODS The expression of HIF-1alpha was detected by immunohistochemical analysis. Functional studies of HIF in medulla were carried out by gene transfer of various plasmids by retrograde injection via ureter. RESULTS Our immunohistochemical analysis detected HIF-1alpha in the inner stripe and the inner medulla of normal rats. Water deprivation increased the number of HIF-1alpha-positive cells, which may be mediated by an increase in medullar workload and a decrease in local blood flow. To perform functional studies, we performed gene transfer. Efficient expression of the transgene was confirmed using an enhanced green fluorescent protein (E-GFP) expressing vector. Our histologic and immunoblotting analysis detected the transgene product at the inner medulla and the inner stripe 48 hours after injection. Administration of negative-dominant HIF induced severe damage in the medulla of normal rats. In contrast, gene transfer of constitutively active HIF (HIF/VP16) induced expression of various HIF-regulated genes and protected the medulla against ischemic insults. CONCLUSION Our studies demonstrated a crucial role of HIF in the renal medulla under normal and hypoxic circumstances.
Evaluating the effectiveness of different approaches to home support for people in later stage dementia: a protocol for an observational study

ABSTRACT Background: Dementia is a major health problem with a growing number of people affected by the condition, both directly and indirectly through caring for someone with dementia. Many live at home but little is known about the range and intensity of the support they receive. Previous studies have mainly reported on discrete services within a single geographical area. This paper presents a protocol for study of different services across several sites in England. The aim is to explore the presence, effects, and cost-effectiveness of approaches to home support for people in later stage dementia and their carers. Methods: This is a prospective observational study employing mixed methods. At least 300 participants (people with dementia and their carers) from geographical areas with demonstrably different ranges of services available for people with dementia will be selected. Within each area, participants will be recruited from a range of services. Participants will be interviewed on two occasions and data will be collected on their characteristics and circumstances, quality of life, carer health and burden, and informal and formal support for the person with dementia. The structured interviews will also collect qualitative data to explore the perceptions of older people and carers. Conclusions: This national study will explore the components of appropriate and effective home support for people with late stage dementia and their carers. It aims to inform commissioners and service providers across health and social care.
Accuracy of the Canadian C-spine rule and NEXUS to screen for clinically important cervical spine injury in patients following blunt trauma: a systematic review

Background: There is uncertainty about the optimal approach to screen for clinically important cervical spine (C-spine) injury following blunt trauma. We conducted a systematic review to investigate the diagnostic accuracy of the Canadian C-spine rule and the National Emergency X-Radiography Utilization Study (NEXUS) criteria, 2 rules that are available to assist emergency physicians to assess the need for cervical spine imaging. Methods: We identified studies by an electronic search of CINAHL, Embase and MEDLINE. We included articles that reported on a cohort of patients who experienced blunt trauma and for whom clinically important cervical spine injury detectable by diagnostic imaging was the differential diagnosis; evaluated the diagnostic accuracy of the Canadian C-spine rule or NEXUS or both; and used an adequate reference standard. We assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies criteria. We used the extracted data to calculate sensitivity, specificity, likelihood ratios and post-test probabilities. Results: We included 15 studies of modest methodologic quality. For the Canadian C-spine rule, sensitivity ranged from 0.90 to 1.00 and specificity ranged from 0.01 to 0.77. For NEXUS, sensitivity ranged from 0.83 to 1.00 and specificity ranged from 0.02 to 0.46. One study directly compared the accuracy of these 2 rules using the same cohort and found that the Canadian C-spine rule had better accuracy. For both rules, a negative test was more informative for reducing the probability of a clinically important cervical spine injury. Interpretation: Based on studies with modest methodologic quality and only one direct comparison, we found that the Canadian C-spine rule appears to have better diagnostic accuracy than the NEXUS criteria. Future studies need to follow rigorous methodologic procedures to ensure that the findings are as free of bias as possible.