Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic, Biochemical, and Transcriptional Responses of Saccharomyces cerevisiae to the Novel Immunomodulator FTY720 Largely Mimic Those of the Natural Sphingolipid Phytosphingosine*

Sphingolipids are signaling molecules that influence diverse cellular functions from control of the cell cycle to degradation of plasma membrane proteins. The synthetic sphingolipid-like compound FTY720 is an immunomodulating agent in clinical trials for transplant graft maintenance. In this report, we compare the effects of the natural yeast sphingolipid phytosphingosine with FTY720 in Saccharomyces cerevisiae. We show that the multicopy suppressor genes that induce growth resistance to FTY720 also confer resistance to growth-inhibitory concentrations of phytosphingosine. In addition, mutants for ubiquitination pathway proteins are shown to be resistant to the growth-inhibiting effect of both FTY720 and phytosphingosine. We observe fewer similarities between sphingosine and FTY720 than between FTY720 and phytosphingosine as revealed by genetic studies. Yeast cells lacking the specific sphingosine kinase LCB4 are sensitive to phytosphingosine and FTY720 but resistant to sphingosine, suggesting that FTY720 and phytosphingosine have a more related mechanism of action. Gene expression profile comparisons of sensitive and resistant yeast cells exposed to FTY720 and phytosphingosine highlight a number of similarities. In response to treatment with these compounds, ∼77% of the genes that are regulated >2-fold by FTY720 also respond to phytosphingosine in the same direction in the parent strain. In addition, a close inspection of TAT1 and TAT2 transporters following exposure to phytosphingosine indicates that TAT1 protein is degraded in a similar fashion upon treatment with FTY720 and phytosphingosine. There were differences, however, with respect to the TAT2 protein level and the expression profiles of a subset of genes. The genetic, transcriptional, and biochemical data together indicate that FTY720 and phytosphingosine influence similar pathways in yeast cells. These findings offer further insights into the physiological pathways influenced by these compounds in all eukaryotic cells and help us to understand the therapeutic consequences of FTY720 in humans.
A longitudinal study of ammonia, acetone and propanol in the exhaled breath of 30 subjects using selected ion flow tube mass spectrometry, SIFT-MS

Selected ion flow tube mass spectrometry, SIFT-MS, has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 males, 11 females) over a 6 month period. Volunteers provided breath samples each week between 8:45 am and 1 pm (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ammonia, acetone and propanol. It was found that the concentration distributions of these compounds in breath were close to log-normal. The median ammonia level estimated as a geometric mean for all samples was 833 parts per billion (ppb) with a multiplicative standard deviation of 1.62, the values ranging from 248 to 2935 ppb. Breath ammonia clearly increased with increasing age in this volunteer cohort. The geometric mean acetone level for all samples was 477 parts per billion (ppb) with a multiplicative standard deviation of 1.58, the values ranging from 148 to 2744 ppb. The median propanol level for all samples was 18 ppb, the values ranging from 0 to 135 ppb. A weak but significant correlation between breath propanol and acetone levels is apparent in the data. The findings indicate the potential value of SIFT-MS as a non-invasive breath analysis technique for investigating volatile compounds in human health and in the diseased state.
The treatment of mycosis fungoides. Adjuvant topical mechlorethamine after electron beam therapy

The feasibility of employing adjuvant topical mechlorethamine after electron beam therapy in the treatment of patients with mycosis fungoides is demonstrated. Patients treated with a planned adjuvant topical mechlorethamine schedule had a median disease‐free interval of 25 months compared to 17 months for the group treated with electron beam therapy alone. Projected relapse‐free survivals are slightly better in the adjuvant group—37% versus 29%. Patients receiving adjuvant topical mechlorethamine after the electron beam were observed to have a low incidence of contact allergy to the medication. The topical medication can be continued if a contact allergy develops by using a planned desensitization program. We currently treat all mycosis fungoides patients with electron beam therapy randomizing half to receive adjuvant topical mechlorethamine. Cancer 40:2851‐2853, 1977.
Investments in ESG-Rated Mutual Funds: Is Good Better than Great?

Socially responsible mandated mutual funds are a popular class of funds characterized by strategies that address sustainability, responsibility, and impact. The dramatic growth of socially responsible mandated mutual funds during the last decade, makes it important to understand how their social metrics (environmental, social, and governance; ESG) relates to their financial performance. This article compares the risk-adjusted returns of socially responsible mutual funds (SRMF) with funds rated by Morningstar® Portfolio ESG ScoreTM grouped into low, medium, and high ratings. We find that during the period of pre-recession boom, the funds with high-ESG ratings had a significantly higher risk-adjusted performance than did funds with a low-ESG or mid-ESG rating. This trend continued during the early parts of the Great Recession. During periods of economic recovery and growth, SRMF rated low on ESG performed significantly better than highly rated SRMFs. For medium rated SRMFs, other than prior to the Great Recession, fund performance was not consistently significantly different from highly rated SRMFs.
Management control packages: a literature review and guidelines for public sector research

ABSTRACT The effectiveness of a management control (MC) element, such as performance measurement, may depend on other MC elements, such as organizational values and training activities. This is why MC elements should be studied ‘as a package’, instead of as isolated elements. Although examining MC elements as a package has the potential to make significant contributions to ongoing debates, this approach is largely absent in the academic public sector management literature. This paper reviews the MC package literature, examines its implications for public sector research and practice, and aids future research by discussing research design choices and research directions. IMPACT Management control (MC) elements can be used to motivate employees to act in line with organizational goals. The effectiveness of an MC element, such as a performance measure, can depend on other MC elements that are used in an organization, such as result-oriented values and training for new hires. This is why managers should contemplate the potential interplay of an MC element with other elements when they consider implementing, removing or examining the effectiveness of an MC element. This paper identifies barriers that may complicate the study of MC packages in the public sector, and presents guidelines and practical tips on how to overcome these potential barriers.
The C-terminal domain of p53 orchestrates the interplay between non-covalent and covalent poly(ADP-ribosyl)ation of p53 by PARP1

Abstract The post-translational modification poly(ADP-ribosyl)ation (PARylation) plays key roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose) binding and covalent PARylation control protein functions, however, it is unknown how the two modes of modification crosstalk mechanistically. Employing the tumor suppressor p53 as a model substrate, this study provides detailed insights into the interplay between non-covalent and covalent PARylation and unravels its functional significance in the regulation of p53. We reveal that the multifunctional C-terminal domain (CTD) of p53 acts as the central hub in the PARylation-dependent regulation of p53. Specifically, p53 bound to auto-PARylated PARP1 via highly specific non–covalent PAR-CTD interaction, which conveyed target specificity for its covalent PARylation by PARP1. Strikingly, fusing the p53-CTD to a protein that is normally not PARylated, renders this a target for covalent PARylation as well. Functional studies revealed that the p53–PAR interaction had substantial implications on molecular and cellular levels. Thus, PAR significantly influenced the complex p53–DNA binding properties and controlled p53 functions, with major implications on the p53-dependent interactome, transcription, and replication-associated recombination. Remarkably, this mechanism potentially also applies to other PARylation targets, since a bioinformatics analysis revealed that CTD-like regions are highly enriched in the PARylated proteome.
HLA‐A, ‐B and ‐DRB1 polymorphism in Koreans defined by sequence‐based typing of 4128 cord blood units

Human leucocyte antigen (HLA) alleles and haplotypes differ significantly among different ethnic groups, and high‐resolution typing methods allow for the detection of a wider spectrum of HLA variations. In this study, HLA‐A, ‐B and ‐DRB1 genotypes were analysed in 4128 cord blood units obtained from Korean women using the sequence‐based typing method. A total of 44 HLA‐A, 67 HLA‐B and 48 HLA‐DRB1 most probable alleles were identified. Of these, high‐frequency alleles found at a frequency of ≥5% were 6 HLA‐A (A*02:01, A*02:06, A*11:01, A*24:02, A*31:01, A*33:03), 5 HLA‐B (B*15:01, B*44:03, B*51:01, B*54:01, B*58:01) and 7 HLA‐DRB1 (DRB1*01:01, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01) alleles. At each locus, A*02, B*15 and DRB1*04 generic groups were most diverse at allelic level, consisting of 8, 11 and 10 different alleles, respectively. Two‐ and three‐locus haplotypes estimated by the maximum likelihood method revealed 73 A‐B, 74 B‐DRB1 and 42 A‐B‐DRB1 haplotypes with frequencies of ≥0.3%. A total of 193 A‐B‐DRB1 haplotypes found at a frequency of ≥0.1% were presented, and the six most common haplotypes were A*33:03‐B*44:03‐DRB1*13:02 (4.6%), A*33:03‐B*58:01‐DRB1*13:02 (3.0%), A*24:02‐B*07:02‐DRB1*01:01 (2.7%), A*33:03‐B*44:03‐DRB1*07:01 (2.5%), A*30:01‐B*13:02‐DRB1*07:01 (2.2%) and A*24:02‐B*52:01‐DRB1*15:02 (2.1%). Compared with previous smaller scale studies, this study further delineated the allelic and haplotypic diversity in Koreans including low‐frequency alleles and haplotypes. Information obtained in this study will be useful for the search for unrelated bone marrow donors and for anthropologic and disease association studies.
Clinical predictors of driving status in Huntington's disease

The aim of this study was to identify the motor, cognitive, and behavioral determinants of driving status and risk factors for driving cessation in Huntington's disease (HD). Seventy‐four patients with HD were evaluated for cognitive, motor, psychiatric, and functional status using a standardized battery (Unified Huntington's Disease Rating Scale [UHDRS] and supplemental neuropsychological testing) during a research clinic visit. Chart review was used to categorize patients into two driving status categories: (1) “currently driving” included those driving and driving but with clinician recommendation to restrict, and (2) “not driving” included those with clinician recommendation to cease driving and those not currently driving because of HD. Multi‐ and univariate logistic regression was used to identify significant clinical predictors of those driving versus not driving. Global cognitive performance and UHDRS Total Functional Capacity scores provided the best predictive model of driving cessation (Nagelkerke R2 = 0.65; P < 0.0001). Measures of learning (P = 0.006) and psychomotor speed/attention (P = 0.003) accounted for the overall cognitive finding. In univariate analyses, numerous cognitive, motor, and daily functioning items were significantly associated with driving. Although driving status is associated with many aspects of the disease, results suggest that the strongest association is with cognitive performance. A detailed cognitive evaluation is an important component of multidisciplinary clinical assessment in patients with HD who are driving. © 2012 Movement Disorder Society
Analysis of treatment failure after radiosurgery for arteriovenous malformations.

OBJECT The aim of this study was to evaluate the causes of treatment failure in patients with arteriovenous malformations (AVMs) who underwent radiosurgery, which is increasingly used as a treatment method for selected, surgically high-risk AVMs. Unfortunately, radiosurgical treatment fails in a small but significant percentage of patients. In the time period covered in this study, 72 patients attained angiographically confirmed cures after radiosurgery and 36 were retreated after the initial radiosurgical treatment failed. METHODS Using a computerized image fusion technique, the initial radiosurgical dosimetry plan was superimposed on the remaining AVM nidus at the time of retreatment. Twenty-six percent of the retreated cases were found to have AVM niduses outside the original treatment isodose line, which means that targeting error was a factor. The retreated group was also statistically compared with the cured group. CONCLUSIONS Multivariate analysis revealed that the following factors were statistically significant predictors of treatment failure: increasing AVM size, decreasing treatment dose, and increasing Spetzler-Martin grade.
Optical PUF for Vehicles Non-Forwardable Authentication ( Extended Version )

Modern vehicles are configured to exchange warning messages through IEEE 1609 Dedicated Short Range Communication over IEEE 802.11p Wireless Access in Vehicular Environment. However, these warning messages must associate an authentication factor such that verifier authenticates the message origin via visual binding. Apparently, vehicle to vehicle communication is vulnerable to message forwarding and thereby allowing an incorrect visual binding with the malicious vehicle. We introduce the non-forwardable authentication to avoid the adversary coalition attack scenario for a secure vehicle to vehicle communication. Accordingly, the group of adversaries impose fabricated vehicle attributes in order to impersonate the intended sender and reroute the eavesdropped messages. Therefore, the verifier misidentify one of these adversaries as the authentic vehicle instead of actual sender. We propose to utilize spontaneous optical response verification and establish a session secret key with the original remote vehicle, exchanging messages routed through a resembling and adversarial vehicle. Thus, the communicating parties identify another vehicle as the one they secretly communicate with over wireless radio channel, which in turn can cause hazardous situations. These optical response are generated through hardware means such as a certified Physically Unclonable Function (PUF) device embedded on front and rear of the vehicle and must be verified against a pre-certified fresh pairs of challenges and responses, for the same vehicle. Furthermore, vehicles utilize an out-of-band optical communication channel to exchange the physically unclonable function stimulated optical challenge and corresponding response from the sender and receiver, respectively. It is important to mention that the pre-certified response must be verified against a certified physically unclonable function stimulated immediate optical response rather the image of pre-recorded optical response, for the specific peer vehicle. To the best of our knowledge, this is the first work proposing a solution based on physically unclonable function for a secure non-forwardable vehicle to vehicle authentication.
A hybrid intra refresh and reference selection scheme for mobile video coding

Real-time video performance is difficult to guarantee under mobile communication environments characterized by loss-probability-varying transmission channel, heterogeneous networks, and various mobile devices of different access capabilities. In this paper, a novel attention-based network-aware robust video coding scheme mixing adaptive intra refresh with reference picture selection is proposed to improve the visual experience for mobile video. This method unifies human visual attention, state information of wireless channel and hybrid refresh tools to realize optimum bitrate allocation so that uneven robustness for attentive image regions against the packet loss can be readily accomplished. Further, a set of tools serving for evaluating the refresh regions, refresh modes and reference decision are developed, considering a balance among the coding efficiency, error resilience and user experience. Experiments on H.264 show that the proposed scheme provides a much better subjective feeling than traditional refresh methods when compressed video is delivered over wireless channels.
Effect of Voltage Transformation Ratio on the Kilovoltampere Rating of Delta-Connected Autotransformer for 12-Pulse Rectifier System

This paper presents the effect of voltage transformation ratio on the kilovoltampere rating of delta-connected autotransformer for 12-pulse rectifier system and gives an optimal configuration of the autotransformer with minimal kilovoltampere rating and the least windings. According to the phasor diagrams and the relation between the output voltage and input voltage of the autotransformer under different connection ways, the effect of voltage transformation ratio on current through windings is analyzed, and corresponding expressions and waveforms of the currents are also obtained. Consequently, a relation between the position parameter and output power is established, and based on the relation, the effect of winding configuration on the kilovoltampere rating of the autotransformer is analyzed, which can be used to obtain the optimal configuration. From the theoretical analysis, an autotransformer with optimal configuration and minimal equivalent kilovoltampere rating is designed. Some simulated and experimental results show the correctness of the theoretical analysis.
Viral Modulators of Cullin RING Ubiquitin Ligases: Culling the Host Defense

Cullin RING ubiquitin ligases (CRULs) are found in all eukaryotes and play an essential role in targeting proteins for ubiquitin-mediated destruction, thus regulating a plethora of cellular processes. Viruses manipulate CRULs by redirecting this destruction machinery to eliminate unwanted host cell proteins, thus allowing viruses to slip past host immune barriers. Depending on the host organism, virus-modified CRULs can perform an amazing range of tasks, including the elimination of crucial signal transduction molecules in the human interferon pathway and suppression of virus-induced gene silencing in plants. This Perspective summarizes recent advances in our understanding of how viral proteins manipulate the function of CRULs.
Union Threat Effects and the Decline in Employer-Provided Health Insurance

Employer-provided health insurance decreased by an average of almost 0.6 percentage points per year for adults aged 18 to 64 who were working full-time in the private sector between 1983 and 2007. Most of this decline was among non-union workers. This study reports estimates that suggest the decrease was caused by a decline employers faced in the threat of being unionized, as measured by the drop in state-level private-sector union density over the 25 years and across the 50 states. The author hypothesizes the decline in union density caused some non-union employers to decide not to offer health insurance. The study shows the importance of accounting for measurement error in union density when estimating the declining threat effect of unionization on non-union employer-provided health insurance coverage.
Controlling Dengue: Effectiveness of Biological Control and Vaccine in Reducing the Prevalence of Dengue Infection in Endemic Areas

With the increased prevalence of dengue infection in tropical countries, concerned members of the public are now pressing their local health ministries to act immediately and effectively in managing the rising numbers of reported cases. This includes reviews of the methodologies and the effectiveness of current combative systems to find other possible novel approaches that might yield better results. One of those novel approaches is the integration of a parasite into mosquito vector, manipulating the parasite-host interaction to reduce the transmission of dengue in endemic hotspots. Another alternative is by Sanofi-Pasteur’s dengue vaccine that showed over 60.8% success rate in reducing severe dengue infection in children aged 9 - 16 during its final clinical implementation phase. This report will compare and contrast these two novel ideas to determine which of the approaches are more likely to be effective in the long run. The aspects covered will include the application, effectiveness, functionality, and problems with these approaches. The results could then be utilised by governments or organizations to select precise and effective methods in reducing the prevalence of dengue infections in their countries.
Immunoblot analysis of humoral immune responses following infection with Bordetella pertussis or immunization with diphtheria-tetanus-pertussis vaccine

To help develop better diagnostic tests for pertussis, we examined the serologic response to whole-cell proteins of Bordetella pertussis after natural infection or vaccination with diphtheria-tetanus-pertussis vaccine. Serum specimens collected during a pertussis outbreak investigation and from uninfected persons were used in Western blot (immunoblot) analyses to determine the presence of immunoglobulin G (IgG) and IgA antibodies to specific B. pertussis proteins. IgG antibodies to proteins of molecular masses 220 and 210 kilodaltons (kDa) were detected in 14 of 18 serum samples obtained from patients with culture-confirmed pertussis greater than or equal to 40 days after the onset of coughing. IgA antibodies were detected in 15 of the 18 samples. Of 19 serum samples obtained from patients who had not been ill with pertussis, 6 contained IgG antibodies to these proteins and 1 contained IgA antibodies. The two proteins bound antiserum specific for filamentous hemagglutinin and comigrated with purified filamentous hemagglutinin. IgG antibodies to two additional protein bands of molecular masses 84 and 75 kDa were associated with previous vaccination. Antibody to the 84-kDa protein was detected in 15 of 17 vaccinated, never-infected persons, and antibody to the 75-kDa protein was detected in 16 of the 17. None of 11 nonvaccinated, never-infected persons tested had antibodies to either protein. All seven fully vaccinated persons with culture-documented infection had antibodies to both proteins. Antibodies to the 84-kDa protein were detected in 6 of 22 nonvaccinated and infected persons, and antibodies to the 75-kDa protein were detected in 8 of the 22. Use of Western blot analysis in this study allowed us to distinguish antibody responses to infection and immunization.
Counting Cytokinesis Proteins Globally and Locally in Fission Yeast

We used fluorescence microscopy to measure global and local concentrations of 28 cytoskeletal and signaling proteins fused to yellow fluorescent protein (YFP) in the fission yeast Schizosaccharomyces pombe. Native promoters controlled the expression of these functional YFP fusion proteins. Fluorescence measured by microscopy or flow cytometry was directly proportional to protein concentration measured by quantitative immunoblotting. Global cytoplasmic concentrations ranged from 0.04 (formin Cdc12p) to 63 micromolar (actin). Proteins concentrated up to 100 times in contractile rings and 7500 times in spindle pole bodies at certain times in the cell cycle. This approach can be used to measure the global and local concentrations of any fusion protein.