Miracle-dz/UniFAR-FTUs huggingface dataset:
Elimination of Channel-Forming Activity by Insertional Inactivation of the p13 Gene in Borrelia burgdorferi

ABSTRACT P13 is a chromosomally encoded 13-kDa integral outer membrane protein of the Lyme disease agent, Borrelia burgdorferi. The aim of this study was to investigate the function of the P13 protein. Here, we inactivated the p13 gene by targeted mutagenesis and investigated the porin activities of outer membrane proteins by using lipid bilayer experiments. Channel-forming activity was lost in the p13 mutant compared to wild-type B. burgdorferi, indicating that P13 may function as a porin. We purified native P13 to homogeneity by fast performance liquid chromatography and demonstrated that pure P13 has channel-forming activity with a single-channel conductance in 1 M KCl of 3.5 nS, the same as the porin activity that was lost in the p13 mutant. Further characterization of the channel formed by P13 suggested that it is cation selective and voltage independent. In addition, no major physiological effects of the inactivated p13 gene could be detected under normal growth conditions. The inactivation of p13 is the first reported inactivation of a gene encoding an integral outer membrane protein in B. burgdorferi. Here, we describe both genetic and biophysical experiments indicating that P13 in B. burgdorferi is an outer membrane protein with porin activity.
Uncertainty Shocks and Dynamic Compensation∗

This paper studies optimal dynamic compensation when firms are subject to uncertainty shocks but have only limited ability to commit to long-term contracts. I analyze a continuous-time dynamic principal-agent model with private effort and regime switching in cash flow volatility and characterize the optimal managerial compensation and termination policy. In high volatility times, firms are forced to expedite payments to managers because sufficient deferred compensation is no longer credible. At the same time, contract length shortens, that is, termination becomes more likely. This relation between the timing of payments and expected contract length may explain the sizeable cash bonuses observed in crises times. In contrast, with full commitment firms defer compensation more when volatility is high. JEL Classification: D86, M12, G34
Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer.

PURPOSE Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC. PATIENTS AND METHODS Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC. RESULTS Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates (P < .0001) and 3-year overall survival (OS) rates (P < .0001). TNBC was associated with increased risk for visceral metastases (P = .0005), lower risk for bone recurrence (P = .027), and shorter postrecurrence survival (P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival (P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC (P < .0001). CONCLUSION Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.
The binding epitopes of neurotrophin‐3 to its receptors trkC and gp75 and the design of a multifunctional human neurotrophin.

Survival and maintenance of vertebrate neurons are influenced by neurotrophic factors which mediate their signal by binding to specific cell surface receptors. We determined the binding sites of human neurotrophin‐3 (NT‐3) to its receptors trkC and gp75 by mutational analysis and compared them to the analogous interactions of nerve growth factor (NGF) with trkA and gp75. The trkC binding site extends around the central beta‐strand bundle and in contrast to NGF does not make use of non‐conserved loops and the six N‐terminal residues. The gp75 epitope is dominated by loop residues and the C‐terminus of NT‐3. A novel rapid biological screening procedure allowed the identification of NT‐3 mutants that are able to signal efficiently through the non‐preferred receptors trkA and trkB, which are specific for NGF and BDNF respectively. Mutation of only seven residues in NT‐3 resulted in a human neurotrophin variant which bound to all receptors of the trk family with high affinity and efficiently supported the survival of NGF‐, BDNF‐ and NT‐3‐dependent neurons. Our results suggest that the specificity among neurotrophic factors is not solely encoded in sequence diversity, but rather in the way each neurotrophin interacts with its preferred receptor.
Understanding the factors behind the decision to purchase varying coverage amounts of long-term care insurance.

OBJECTIVE This article examines the factors related to an individual's decision to purchase a given amount of long-term care insurance coverage. DATA SOURCE AND STUDY SETTING: Primary data analyses were conducted on an estimation sample of 6,545 individuals who had purchased long-term care (LTC) insurance policies in late 1990 and early 1991, and 1,248 individuals who had been approached by agents but chose not to buy such insurance. Companies contributing the two samples represented 45 percent of total sales during the study year. STUDY DESIGN A two-stage logit-OLS (ordinary least squares) choice-based sampling model was used to examine the relationship between the expected value of purchased coverage and explanatory variables that included: demographic traits, attitudes, risk premium, nursing home bed supply, and Medicaid program configurations. DATA COLLECTION Mail surveys were used to collect information about individuals' reasons for purchase, attitudes about long-term care, and demographic characteristics. Through an identification code, information on the policy designs chosen by these individuals was linked to each of the returned mail surveys. The response rate to the survey was about 60 percent. PRINCIPAL FINDINGS The model explains about 47 percent of the variance in the dependent variable-expected value of policy coverage. Important variables negatively associated with the dependent variable include advancing age, being married, and having less than a college education. Variables positively related include being male, having more income, and having increasing expected LTC costs. Medicaid program configuration also influences the level of benefits purchased: state reimbursement rates and the presence of comprehensive estate recovery programs are both positively related to the expected value of purchased benefits. Finally, as the difference between the premium charged and the actuarially fair premium increases, individuals buy less coverage. CONCLUSIONS An important finding with implications for policymakers is that changes in Medicaid policy affect the decisions of consumers regarding the acquisition of private LTC policies as well as the level of protection chosen. This is particularly important to states interested in pursuing public-private partnerships in long-term care financing.
Neuroprotective effects of berry fruits on neurodegenerative diseases

Recent clinical research has demonstrated that berry fruits can prevent age-related neurodegenerative diseases and improve motor and cognitive functions. The berry fruits are also capable of modulating signaling pathways involved in inflammation, cell survival, neurotransmission and enhancing neuroplasticity. The neuroprotective effects of berry fruits on neurodegenerative diseases are related to phytochemicals such as anthocyanin, caffeic acid, catechin, quercetin, kaempferol and tannin. In this review, we made an attempt to clearly describe the beneficial effects of various types of berries as promising neuroprotective agents.
The Effect of Accounting Restatements on Earnings Revisions and the Estimated Cost of Capital

This paper examines the effect of accounting restatements on a firm's cost of equity capital. We show that, on average, accounting restatements lead to both decreases in expected future earnings and increases in the firm's cost of equity capital. Depending on the model used, relative percentage increases in the cost of equity capital average between 7 and 19% in the month immediately following a restatement. The relative increase in the cost of capital dissipates as time passes and after controlling for analyst forecast biases, but continues to average between 6 and 15% in the most conservative setting. We also show that restatements initiated by auditors are associated with the largest increase in the cost of capital, and that firms with greater leverage experience greater increases in their cost of capital. Overall, our evidence is consistent with accounting restatements lowering the perceived earnings quality of the firm and increasing investors' required rates of return.
The effects of ‘supra-physiological’ vitamin B12 administration on temporary threshold shift

The aim of this study was to evaluate, in 20 young volunteer subjects, the effects of supra-physiological vitamin B12 administration on noise-induced temporary threshold shift (TTS). All subjects had hearing thresholds within 15dBHL and type A tympanograms. The subjects were randomly assigned to two different groups. Experimental group subjects received cyanocobalamin, 1 mg daily for 7 days, and 5 mg on the eighth day. Control group subjects received a placebo injection daily for 8 days. The vitamin B12 concentration, hearing thresholds and TTS2 (10 min of exposure, narrowband noise centred at 3 kHz, bandwidth of 775 Hz, 112 dB SPL) were measured before and 8 days after treatment. At the end of treatment, the serum vitamin B12 concentration was significantly increased in the experimental group. After 8 days of treatment, the control group showed the same hearing thresholds and TTS2 degrees. Statistical analysis showed that TTS2 decreased significantly at 3 and 4 kHz when cobalamin was used to increase the serum concentration of vitamin B12 to >2350 pg/ml. In addition, a protective effect at 3 kHz in the experimental group was evident when compared with the placebo group. These results suggest that elevated plasma cyanocobalamin levels may reduce the risk of hearing dysfunction resulting from noise exposure in healthy, young subjects. Sumario El propósito de este estudio fue evaluar, en 20 sujetos voluntarios jóvenes, los efectos de la administración supra-fisiológica de vitamina B12 sobre el cambio temporal de los umbrales auditivos inducido por ruido (TTS). Todos los sujetos tenían umbrales auditivos alrededor de 15 dB HL y timpanogramas tipo “A”, y fueron distribuidos al azar en dos grupos diferentes. Los sujetos del grupo experimental recibieron 1 mg diario de cianocobalamina por 7 días, y 5 mg en el octavo día. Los sujetos del grupo control recibieron una inyección diaria de placebo por 8 días. La concentración de vitamina B12, el umbral auditivo y el TTS2 (10 minutos de exposición, ruido de banda estrecha centrado en 3 kHz, ancho de banda de 775 Hz, 112 dB SPL) se midieron antes del tratamiento y 8 días después del mismo. Al final del tratamiento, la concentración sérica de vitamina B12 estaba significativamente elevada en el grupo experimental. Luego de 8 días de tratamiento, el grupo control mostró los mismos umbrales auditivos y grados de TTS2. El análisis estadístico mostró que el TTS2 disminuyó significativamente en 3 y 4 kHz, cuando se utilizó la cianocobalamina para aumentar las concentraciones séricas de vitamina B12 hasta>2350pg/ml. Además, fue evidente un efecto protector en 3 kHz en el grupo experimental cuando se comparó con el grupo placebo. Estos resultados sugieren que los niveles plasmáticos elevados de cianocobalamina pueden reducir el riesgo de disfunción auditiva como resultado de la exposición al ruido, en sujetos jóvenes sanos.
LES for wind load estimation by unstructured grid system

ABSTRACT: Recent development of high-performance computers and techniques on computational fluid engineering has enabled us to simulate the complicated flow such as the wind in urban area. Large Eddy Simulation (LES) is expected to be adopted as an effective technique to evaluate wind load on buildings for wind-resistant design. In this research, the accuracy of LES to evaluate surface pressures on the 3D square cylinder model is examined. Especially, the availability of LES using unstructured grid system is studied to estimate fluctuating as well as mean component of pressures by comparison with experimental results. The computed results correlate highly with the experiments, including the case of a square cylinder with angle of attack for wind direction which introduces a local negative pressure on the side.
Does Feeding Competition Influence Tammar Wallaby Time Allocation

Animals may aggregate to reduce predation risk, but this potentially incurs the cost of increased competition. We studied the degree to which competition for food influenced the time tammar wallabies (Macropus eugenii) allocate to foraging and vigilance by experimentally manipulating access to food, while holding other factors constant. Groups of six wallabies were observed when they had access to either one or six non-depleting bins of supplemental food. Food availability had no effect on the time allocated to foraging, looking or affiliative interactions, and this was true whether individuals or groups were treated as the unit of analysis. However, wallabies engaged in substantially more aggressive acts in the high-competition treatment. These results, when combined with other findings, suggest that the moderately social tammar wallaby receives an antipredator benefit by aggregating with conspecifics which is not reduced significantly by foraging competition.
THE ABC'S of Mice

This is the introductory half of a lecture given at the Association for Symbolic Logic Annual Meeting in Philadelphia in March, 2001. Our goal is to give logicians and advanced students who are unfamiliar with inner model theory a taste of what the subject is about at a level where it is possible to say something meaningful about the intuitions and proofs. At the same time, we wish to avoid overwhelming the reader, so we will leave out many well known closely related theorems and give only short proof sketches. Neither the results nor the proofs found here are due to the author. We will begin near the beginning but still touch on some modern aspects of the theory. The proofs and historical notes that we leave out can be found in the books and articles listed in the references. Our approach to the theory of 0# is a combination of that taken by Dodd in his book and by Steel in his lectures to students. Dodd's introduction is one of the author's favorite essays on inner model theory; another is the introduction to Martin-Steel [6]. In Section 2, we review the theory of 0# in a form that touches on some of the techniques that have been and continue to be generalized. These combine what is commonly called iteration and fine structure. In Section 3, we give a superficial description of what comes after 0#. Those interested in learning about more recent developments in inner model theory are encouraged to see the articles Lowe-Steel [5] and Steel [8], both of which are currently available online at http://www.math.berkeley.edu/~ steel.
Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia

The influence of driver mutations on leukaemic transformation was analysed in 1747 patients with polycythaemia vera or essential thrombocythaemia. With a median follow‐up of 7·2 years, 349 patients died and 62 progressed to acute leukaemia or myelodysplastic syndrome. Taking death as a competing risk, CALR genotype was associated with a lower risk of transformation [subdistribution hazard ratio (SHR): 0·13, 95% confidence interval (CI): 0·2–0·9, P = 0·039], whereas JAK2 V617F showed borderline significance for higher risk (SHR: 2·05, 95% CI: 0·9–4·6, P = 0·09). Myelofibrotic transformation increased leukaemic risk, except in CALR‐mutated patients. Next generation sequencing of 51 genes at the time of transformation showed additional mutations (median number: 3; range: 1–5) in 25 out of 29 (86%) assessable cases. Mutations (median: 1; range: 1–3) were detected in 67% of paired samples from the chronic phase. Leukaemia appeared in a JAK2 V617F negative clone in 17 (58%) cases, eleven of them being previously JAK2 V617F‐positive. JAK2 V617F‐mutated leukaemia was significantly associated with complex karyotype and acquisition of TP53 mutations, whereas EZH2 and RUNX1 mutations were more frequent in JAK2 V617F‐negative leukaemia. Survival was longer in JAK2 V617F‐unmutated leukaemia (343 days vs. 95 days, P = 0·003). In conclusion, CALR genotype is associated with a lower risk of leukaemic transformation. Leukaemia arising in a JAK2 V617F‐negative clone is TP53 independent and shows better survival.
Bactericidal activities of antibiotics against vancomycin-resistant Enterococcus faecium blood isolates and synergistic activities of combinations

The effects of teicoplanin (8 micrograms/ml), ampicillin (64 micrograms/ml), imipenem (32 micrograms/ml), and gentamicin (4 micrograms/ml), alone and in combination, against 13 unique blood isolates of vancomycin-resistance (MIC for 90% of isolates tested [MIC90], 512 micrograms/ml), teicoplanin-susceptible (MIC90, 2.0 micrograms/ml), ampicillin-resistant (MIC90, 128 micrograms/ml), and non-beta-lactamase-producing Enterococcus facium (vancomycin-resistant enterococci [VRE] isolates) were evaluated by time-kill studies. All 13 isolates exhibited high-level resistance to streptomycin; 7 isolates exhibited high-level gentamicin resistance (HLGR). After 24 h of incubation, ampicillin (64 micrograms/ml) combined with gentamicin (4 micrograms/ml) was bactericidal against three of the VRE isolates that did not display HLGR. Synergy between ampicillin and gentamicin was not observed against these isolates. Teicoplanin (8 micrograms/ml) alone was bactericidal at 24 h against five of six VRE isolates that lacked HLGR, but was not bactericidal against any HLGR VRE isolate at that time point. The addition of ampicillin (64 micrograms/ml) or imipenem (32 micrograms/ml) to teicoplanin did not significantly enhance the killing of HLGR VRE isolates as a group (P = 0.335). However, there was a trend toward improved killing of some HLGR VRE isolates by teicoplanin plus imipenem. Vancomycin (32 micrograms/ml) combined with ampicillin (64 micrograms/ml) was neither bactericidal nor synergistic against HLGR VRE isolates. Overall, bactericidal activity was attainable against 7 of 13 VRE isolates at 24 h.
Anatomical changes with age in the heart and ductus arteriosus in the dog after birth

The heart‐weight to body‐weight ratios were calculated for 242 dogs in 11 groups ranging from one day to adult. The base‐apex diameters, internal transverse diameters, external transverse diameters, and the anterior, posterior, lateral, and interventricular septal wall thicknesses were measured in left ventricles of hearts taken from 45 animals of nine different age groups. The ductus arteriosus was examined for patency in all puppies.
The family history method: whose psychiatric history is measured?

OBJECTIVE The family history method, in which an informant is asked about the history of psychiatric illness in relatives, is widely used in psychiatric research. Previous research has examined the influence on family history information of characteristics of the relative. In this report, the authors seek to clarify the impact on family history reporting of the psychiatric history of the informant. METHOD Both members of female twin pairs from a population-based twin registry were asked about the history of major depression, generalized anxiety disorder, and alcoholism in their mother and father. The authors examined twin pairs discordant for each of the three diagnoses and predicted that the affected twin would report higher rates of the same disorder in her parent than would the unaffected twin. RESULTS Twins with a history of major depression or generalized anxiety disorder but not twins with alcoholism were significantly more likely to report the same disorder in their parents than were their unaffected co-twins. CONCLUSIONS For major depression and generalized anxiety disorder, a family history diagnosis appears to reflect the psychiatric history of both the relative and the informant. Caution may be needed in the interpretation of results based on the family history method, although the magnitude of this problem may be attenuated by the use of multiple informants.
A Rhetorical Analysis of the Discourse of Advertising Herbal Medicine in Southwestern Nigeria

This paper examines the persuasive strategies of advertising herbal medicine in southwestern Nigeria. With recourse to the rhetorical model of analysis, the article identifies and discusses the propaganda techniques/rhetorical strategies in the discourse relative to the herbal medical practitioners' ideological perception of trying to project modern-day herbal healing in Africa as an alternative to that of the failing synthetic drugs of western medical practice. Although the social practice of advertising herbal medicine is culturally based, this study reveals that there are no significant culture-specific strategies of advertising in the data sampled, as the communicative strategies generally fit in with the prefabricated style of advertising discourse. In view of the fact that the advertising genre like other areas of public life is a site of struggle over meaning, the study takes a critical look at the instances of the advertisers' tendency to abuse meaning in language by making certain advertising claims which there is no objective evidence to back up.
Bleeding Colonic Diverticula A Reappraisal of Natural History and Management

ObjectiveThe study was undertaken to correct or reaffirm current recommendations based on old observations of doubtful validity because of their lack of routine colonoscopy, scintigraphy, or angiography. BackgroundPatterns of bleeding were derived from transfusion records of 78 patients admitted 106 times for lower gastrointestinal bleeding with no detectable cause other than colon diverticula. ResultBleeding stopped spontaneously in 82 of 108 episodes and in 66 of 67 patients requiring less than four units of transfusion on any day. When four or more units were required in a day, 25 of 42 patients required emergency surgery. When a bleeding site was identified and removed, only 1 of 25 patients bled again from another divertculum. After discharge without surgery, 28 of 73 began to bled again. After “blind” colectomy and ileoproctostomy, four of seven patients developed leaks or abscesses, and two died. ConclusionsBleeding stopped spontaneously in 75% of episodes and in 99% of patients requiring less than four units of transfusion per day. Bleeding continued in 25% of episodes and in most patients who required four or more units per day. Bleeding sites of those patients who continued to bleed were shown by scintigraphy or angiography. When a bleeding diverticulum is removed, rebleeding is rare. “Blind” resection is unsafe.