Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal Structure of Escherichia coli Diaminopropionate Ammonia-lyase Reveals Mechanism of Enzyme Activation and Catalysis*

Background: DAPAL is a novel PLP-dependent enzyme involved in the degradation of DAP, a nonstandard amino acid. Results: Striking structural differences were observed between apo- and holo-EcDAPAL, and structure with a PLP-aminoacrylate intermediate bound at the active site was obtained. Conclusion: Enzyme undergoes apo to holo structural transitions and follows a two-base mechanism of catalysis. Significance: The results provide insights into the catalytic mechanism of DAPAL. Pyridoxal 5′-phosphate (PLP)-dependent enzymes utilize the unique chemistry of a pyridine ring to carry out diverse reactions involving amino acids. Diaminopropionate (DAP) ammonia-lyase (DAPAL) is a prokaryotic PLP-dependent enzyme that catalyzes the degradation of d- and l-forms of DAP to pyruvate and ammonia. Here, we report the first crystal structure of DAPAL from Escherichia coli (EcDAPAL) in tetragonal and monoclinic forms at 2.0 and 2.2 Å resolutions, respectively. Structures of EcDAPAL soaked with substrates were also determined. EcDAPAL has a typical fold type II PLP-dependent enzyme topology consisting of a large and a small domain with the active site at the interface of the two domains. The enzyme is a homodimer with a unique biological interface not observed earlier. Structure of the enzyme in the tetragonal form had PLP bound at the active site, whereas the monoclinic structure was in the apo-form. Analysis of the apo and holo structures revealed that the region around the active site undergoes transition from a disordered to ordered state and assumes a conformation suitable for catalysis only upon PLP binding. A novel disulfide was found to occur near a channel that is likely to regulate entry of ligands to the active site. EcDAPAL soaked with dl-DAP revealed density at the active site appropriate for the reaction intermediate aminoacrylate, which is consistent with the observation that EcDAPAL has low activity under crystallization conditions. Based on the analysis of the structure and results of site-directed mutagenesis, a two-base mechanism of catalysis involving Asp120 and Lys77 is suggested.
APC mutations in human colorectal adenomas: analysis of the mutation cluster region with temperature gradient gel electrophoresis and clinicopathological features

To date, the earliest mutations in colorectal adenomas have been found in the adenomatous polyposis coli (APC) gene, considered the ‘gatekeeper’ in tumourigenesis. To study the types of APC gene mutations and their relation to clinicopathological features which are associated with malignant potential, the mutation cluster region of the APC gene was analysed in a series of 32 human sporadic colorectal adenomas from 22 patients. DNA was extracted from frozen sections and two overlapping fragments which cover the mutation cluster region were amplified using the polymerase chain reaction (PCR). Mutations were screened with temperature gradient gel electrophoresis and identified by DNA sequencing. Mutations were found in 14 samples (44 per cent) from 11 patients. The changes could be characterized as point mutations (n=7), deletions of one or more nucleotides (n=6), and insertions (n=1). From five patients, multiple adenoma samples were obtained and the adenomas from two of these patients showed a heterogeneous mutation pattern in the APC gene. All detected mutations are predicted to result in a truncated APC protein. Genetic alterations in the mutation cluster region of the APC gene occurred significantly more frequently in large adenomas and showed a trend towards an increase in villous adenomas and adenomas with moderate and severe dysplasia. It is concluded that an increased proportion of APC gene mutations were found in the adenomas showing clinicopathological features associated with increased proliferation but not with characteristics of malignant potential. The results suggest that in a significant proportion of adenomas, other (genetic) alterations are involved in early tumourigenesis. © 1998 John Wiley & Sons, Ltd.
Transcriptome Fingerprint of Bovine 2-Cell Stage Blastomeres Is Directly Correlated with the Individual Developmental Competence of the Corresponding Sister Blastomere1

ABSTRACT To date, gene expression profiles of bovine preimplantation embryos have only been indirectly related to developmental potential due to the invasive nature of such procedures. This study sought to find a direct correlation between transcriptome fingerprint of blastomeres of bovine 2-cell stage embryos with developmental competence of the corresponding sister blastomeres. Isolated blastomeres were classified according to the sister blastomere's development into three groups: two groups displayed developmental incompetency, including those blastomeres whose corresponding sister blastomeres either stopped cleaving after separation (2CB) or were blocked after two additional cleavages before embryonic genome activation (8CB). In the third group were competent blastomeres, which were defined as those whose sister blastomeres developed to the blastocyst stage (BL). As a result, developmental capacity of corresponding sister blastomeres was highly similar. Microarray analysis revealed 77 genes to be commonly differentially regulated among competent and incompetent blastomeres as well as blocked blastomeres. Clustering of differentially expressed genes according to molecular functions and pathways revealed antioxidant activity, NRF2-mediated oxidative stress response, and oxidative phosphorylation to be the main ontologies affected. Expression levels of selected candidate genes were further characterized in an independent model for developmental competence based on the time of first cleavage postfertilization. Moreover, overall results of this study were confirmed by higher developmental rates and more beneficial expression of CAT and PRDX1 when cultured in an antioxidative environment. These results will help us to understand molecular mechanisms defining developmental destination of individual bovine preimplantation embryos.
Efficacy of combination therapy of anti-TNF-α antibody infliximab and methotrexate in refractory entero-Behçet’s disease

It is often difficult to manage refractory gastrointestinal tract complications of Behçet’s disease (entero-BD) by conventional therapy. In this study, we assessed the short- and long-term efficacy and safety of the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-α antibody, and methotrexate in ten patients with refractory entero-BD refractory to conventional therapies. The short- (weeks) and long-term (by 2 years) effects of infliximab at 3–5 mg/kg body weight every 8 weeks on the clinical course and intestinal manifestations were assessed by abdominal computed tomography (CT) and colonoscopy. The primary endpoint was the rate of disappearance of ileocecal ulceration at 12 months of therapy. All patients showed improvement of gastrointestinal symptoms and disease-associated complications within 4 weeks. Furthermore, the rate of disappearance of ileocecal ulcerations was 50% (5/10 patients) at 6 months and 90% (9/10 patients) at 12 months, and, therefore 90% of patients were satisfied with the primary endpoint. Furthermore, corticosteroid dose was significantly reduced from 22.0 to 1.8 mg/day at 24 months. No severe adverse effects were observed during the 24 months of follow-up. We provide evidence for the rapid and excellent efficacy of infliximab in patients with refractory entero-BD and that the combination of infliximab and methotrexate brings about long-term alleviation of entero-BD and excellent tolerability.
The Impact of Bank Branching Deregulations on the U.S. Agricultural Sector

&NA; We demonstrate how states that lifted restrictions on interstate bank expansions, thereby improving access to cheaper credit, experienced increased farm sales and net farm income. In our empirical analysis, we use nationwide county‐level data from 1970 through 2001 and a difference‐in‐differences econometric framework, exploiting only within‐state variation in banking deregulation, to distinguish the effect of an increase in bank competition from potential confounding factors. By including region‐by‐year fixed effects in our econometric equation, we compare changes in farm sales and expenditures in states that lift restrictions on interstate banking to changes in states that do not lift such restrictions within the same census region. Our estimates indicate that county‐level farm sales increase by about 3.4% and county‐level net farm income rises by $1.57 million (in 1982 dollars) after a state deregulates its banking sector by allowing interstate bank expansion. We also find evidence that farm expenditures, in particular expenditures on feed, fuel, machine and equipment rental, as well as interest payments, grew as a result of the banking deregulation. The positive impacts on farm sales, net income, and interest payments are larger in metropolitan counties than in rural counties, consistent with the notion that interstate bank entry following deregulation was concentrated in larger metropolitan markets, leading to a greater reduction in the cost of credit in those areas.
Validation of use of whole-cell repetitive extragenic palindromic sequence-based PCR (REP-PCR) for typing strains belonging to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex and application of the method to the investigation of a hospital outbreak

Acinetobacter spp. are being reported with increasing frequency as causes of nosocomial infection. In order to identify reservoirs of infection as quickly as possible, a rapid typing method that can differentiate epidemic strains from environmental and nonepidemic strains is needed. In 1993, a cluster of Acinetobacter baumannii isolates from five patients in the adult intensive therapy unit of our tertiary-care teaching hospital led us to develop and optimize a rapid repetitive extragenic palindromic sequence-based PCR (REP-PCR) typing protocol for members of the Acinetobacter calcoaceticus-A. baumannii complex that uses boiled colonies and consensus primers aimed at repetitive extragenic palindromic sequences. Four of the five patient isolates gave the same REP-PCR typing pattern as isolates of A. baumannii obtained from the temperature probe of a Bennett humidifier; the fifth isolate had a unique profile. Disinfection of the probe with 70% ethanol, as recommended by the manufacturer, proved ineffective, as A. baumannii with the same REP-PCR pattern was isolated from it 10 days after cleaning, necessitating a change in our decontamination procedure. Results obtained with REP-PCR were subsequently confirmed by ribotyping. To evaluate the discriminatory power (D) of REP-PCR for typing members of the A. calcoaceticus-A. baumannii complex, compared with that of ribotyping, we have applied both methods to a collection of 85 strains that included representatives of six DNA groups within the complex. Ribotyping using EcoRI digests yielded 53 patterns (D = 0.98), whereas 68 different REP-PCR patterns were observed (D = 0.99). By computer-assisted analysis of gel images, 74 patterns were observed with REP-PCR (D = 1.0). Overall, REP-PCR typing proved to be slightly more discriminatory than ribotyping. Our results indicate that REP-PCR typing used boiled colonies is a simple, rapid, and effective means of typing members of the A. calcoaceticus-A. baumannii complex.
Knowledge and Practice of Mothers Regarding the Prevention of Anemia during Pregnancy, in Teaching Hospital, Kathmandu

Iron deficiency anaemia is one of the main causes of anemia during pregnancy as it is associated with increased maternal and perinatal mortality and morbidity. A descriptive and cross-sectional study was carried out to assess the knowledge and practice of mothers regarding the prevention of anemia during pregnancy among mothers who delivered in Tribhuvan University Teaching Hospital (TUTH). Convenient purposive sampling technique was adopted and mothers were included in the study who delivered in TUTH during four weeks period of data collection. They were interviewed by administering semi structured questionnaire. Chi-square test was applied to assess the association between variables. The test result shows that there was significant association in level of knowledge to the educational status regarding prevention of anemia during pregnancy (p=0.002). Furthermore, the study also revealed that there was significant association between frequencies of antenatal care (ANC) visit to the level of knowledge (p=0.007) as well as level of practice (p=0.043) of mothers about prevention of anemia in pregnancy. From the result of the study, it is concluded that the majority of mothers had not adequate knowledge and poor practice regarding prevention of anemia during pregnancy.
INTRAOCULAR TRIAMCINOLONE ACETONIDE FOR PSEUDOPHAKIC CYSTOID MACULAR EDEMA: Optical Coherence Tomography and Multifocal Electroretinography Study

Purpose: To evaluate pseudophakic cystoid macular edema (CME) by optical coherence tomography (OCT) and multifocal electroretinography (mf-ERG) and determine the efficacy of intravitreal triamcinolone acetonide injections. Methods: In this nonrandomized retrospective study, 14 eyes of 14 patients with persistent pseudophakic CME were treated with triamcinolone acetonide injection and were followed up for 1 year. All patients underwent complete ophthalmologic examination including determination of best-corrected visual acuity, slit-lamp examination, tonometry, and funduscopy. Results of OCT and mf-ERG were also recorded before and after the injection. Results: Visual acuity and mf-ERG values increased in all patients after intravitreal triamcinolone acetonide injections. OCT showed improvement of the retinal thickness in the macular area. Temporary increase of intraocular pressure was controlled with topical use of antiglaucoma drops. Conclusion: Intravitreal triamcinolone acetonide injection is a promising therapeutic tool for chronic pseudophakic edema resistant to other medical treatment. However, further study is needed to assess the treatment's long-term efficacy, its safety, and the need for retreatment.
Ultra thin resistively loaded FSS absorber for polarisation independent operation at large incident angles

In this paper we report on a resistively loaded Frequency Selective Surface (FSS) absorber design which is insensitive to the polarization of microwave signals incident at angles of 45o ± 5o. The metal backed periodic structure is composed of an array of conductive rectangular loops, each loaded with a resistor at the center of the four sides. The geometry of the absorber and the resistance value of the vertical and horizontal resistor pairs are carefully chosen so that the structure presents a real impedance of 377 Ω at the center operating frequency for both TE and TM polarized waves incident at 45o. Numerical predictions of the electromagnetic scattering from three different absorbers, designed to work at X-band, are used to investigate the effect of thickness and resistance value on the reflectivity bandwidth and angular sensitivity.
Minimum Wage and Productivity: Evidence from Chilean Manufacturing Plants

This paper analyzes the effects of the minimum wage on a firm’s productivity. The main hypothesis is that an increase in the minimum wage has a negative effect on total factor productivity (TFP) due to the existence of labor adjustment costs. Using data from Chilean manufacturing plants for the period 1992–2005 and a difference-in-differences methodology, we find that an increase in minimum wage had a negative effect on TFP. Our estimates indicate that a real increase of about 22% in the minimum wage during the period 1998–2000 reduced TFP by 5.8% in low unskilled-intensive industries and 9.7% in high unskilled-intensive industries. These results are robust to alternative measures of productivity and to the inclusion of several covariates to avoid confounding effects of other policy changes or firms’ exposure to minimum wage changes.
Auditory attention and selective input modulation: A topographical ERP study

Event-related potentials (ERPs) were recorded in subjects receiving tones (left ear 300 Hz, right ear 6000 Hz) at a rapid rate and trying to detect occasional higher-pitched stimuli in a designated ear. ERPs to attended stimuli showed enhanced negative amplitudes whose topographical distribution differed from that of the exogeneous N1 component. Moreover, the latter was considerably larger for low than high tones, whereas the attention effect had similar amplitudes for the two tones. Consequently, the attention effect, even when perfectly coinciding in time with N1, does not seem to be caused by modulation of the exogeneous N1 but rather by a separate process activated by attention. This suggests that attention does not modulate initial stimulus representations in audition.
Autonomous language learning on Twitter: Performing affiliation with target language users through #hashtags

The purpose of this study is to examine the potential of social networking sites for autonomous language learners, specifically the role of hashtag literacies in learners’ affiliation performances with native speakers. Informed by ecological approach and guided by Zappavigna’s (2012) concepts of `searchable talk` and `ambient affiliation`, the current study employs an autoethnographic approach by analyzing the researcher’s own Twitter experiences in his target language, Spanish, over the period of a year. The participant’s journal, tweets and conversations, and both qualitative and quantitative analysis of the hashtags accompanying tweets show that Twitter has potential to create a space for autonomous learners to enrich their language learning experiences. The thematic analysis of the data further reveals that hashtags, which perform an affiliative function, enable the learner to bond around particular values within authentic discourse communities in his target language. The methodological and practical outcomes of this longitudinal study for second language learning and teaching contexts are also discussed.
Colorectal Carcinoma in Patients under Age 40

Patients under the age of 40 with colorectal cancer (29 females, 18 males) were compared with similar patients in our general hospital population and analyzed for patterns of presentation, stage at diagnosis, degree of tumor differentiation, and survival. There was a higher incidence of poorly differentiated tumors in the young patients (21% vs. 8% in the general population). Colon cancer in young adults was in a more advanced stage at presentation. The survival rate for young patients was 23% vs. 61% for the general population (p = 0.02). Stage C patients treated for cure had a survival rate of 56% in the general population compared with 34% in young adults (p = 0.05). The degree of tumor differentiation did not affect survival in those young patients undergoing curative resections (41% for well-differentiated and 30% for poorly differentiated cancers, p = 0.09). The median survival time by stage was: Stage A and B (N = 3) 36 months, Stage C (N = 26) 32 months, and Stage D (N = 18) 15.8 months. The need for early recognition of colorectal cancer in young adults is emphasized by the greater incidence of advanced disease and the high failure rate.
Comparative analysis of HIV‐1 Tat variants

HIV‐1 Tat protein is a crucial element for viral replication; therefore, its inhibition might be exploited against the AIDS infection. To gain insights on the natural variability of this protein, we present a comparative investigation on the relationship between the primary sequences and the experimentally available three‐dimensional structures from the HIV‐1 Tat variants Z2, BRU, and MAL. Our computational tools include sequence conservation algorithms, structural analysis, electrostatic modeling, and molecular dynamics (MD) simulations. We find that two regions located between residues 10–18 and 41–52 display the highest primary sequence conservation, while the most conserved region among the available structures corresponds approximately to the segment between positions ∼44 and 50. Furthermore, in spite of their large structural divergence, Tat variants share a common mode for long‐range intramolecular interactions. Finally, the flexibility of the Z2, BRU, and MAL variants, as emerging from multinanosecond MD simulations, is rather similar. Based on this work, we conclude that the turnlike region between amino acids 44 and 50 is structurally most conserved, emerging as an important motif for pharmaceutical targeting aimed toward inhibiting Tat action. Proteins 2005. © 2004 Wiley‐Liss, Inc.
Wealth and Income Inequality in America, 1949-2013

Income and wealth inequality in the United States are at historical highs. This paper introduces data from historical waves of the Survey of Consumer Finances (SCF) for the entire post-WW2 period from 1949 to 2013. The new data allow us to add important new aspects to the inequality debate. As the historical household surveys cover the entire balance sheet of households, we can study income and wealth inequality jointly. The data gives us a detailed picture of inequality trends among the bottom 90 %. We document a substantial hollowing out of the middle class as income and wealth concentration at the top was accompanied by losses concentrated in the middle of the distribution. For the first time we can directly contrast the evolution of income and wealth inequality. We show that the income inequality rose earlier and more strongly. We explain this finding by differences in household portfolios. The typical middle-class portfolio is both highly concentrated in housing and highly leveraged. Until the crisis, rising house prices compensated for relative income losses and the growing concentration of financial wealth at the top. Rising middle-class housing wealth gains mitigated the rise in wealth inequality relative to income inequality. The documented differential trends in the evolution of income and wealth inequality provide important information to discriminate between different sources of rising inequality in structural macroeconomic models. Our results highlight the importance of price effects and differences in portfolio composition to understand trends in wealth inequality.
Diversity Aspects of Linear and Decision-Feedback Equalizers for Frequency-Selective Multi-Antenna Channels

The diversity-rate tradeoff was introduced by Zheng and Tse for ML reception in frequency-flat MIMO channels. Since then, some results have been obtained also for the diversity behavior of suboptimal receivers such as linear and decision-feedback equalizers for frequency-selective SIMO channels. However, these results are limited to infinite length equalizers or cyclic prefix systems. In this paper we analyze the diversity of more practical FIR equalizers. We show in particular that linear equalizers lose all frequency diversity in the classical outage-rate trade-off, except at constant rate. Decision-feedback equalizers on the other hand, even if equipped with FIR filters, allow to capture most of the spatiofrequential diversity.