Miracle-dz/UniFAR-FTUs huggingface dataset:
High cell density propionic acid fermentation with an acid tolerant strain of Propionibacterium acidipropionici

Propionic acid is an important chemical with wide applications and its production via fermentation is of great interest. However, economic production of bio‐based propionic acid requires high product titer, yield, and productivity in the fermentation. A highly efficient and stable high cell density (HCD) fermentation process with cell recycle by centrifugation was developed for propionic acid production from glucose using an acid‐tolerant strain of Propionibacterium acidipropionici, which had a higher specific growth rate, productivity, and acid tolerance compared to the wild type ATCC 4875. The sequential batch HCD fermentation at pH 6.5 produced propionic acid at a high titer of ∼40 g/L and productivity of 2.98 g/L h, with a yield of ∼0.44 g/g. The product yield increased to 0.53–0.62 g/g at a lower pH of 5.0–5.5, which, however, decreased the productivity to 1.28 g/L h. A higher final propionic acid titer of >55 g/L with a productivity of 2.23 g/L h was obtained in fed‐batch HCD fermentation at pH 6.5. A 3‐stage simulated fed‐batch process in serum bottles produced 49.2 g/L propionic acid with a yield of 0.53 g/g and productivity of 0.66 g/L h. These productivities, yields and propionic acid titers were among the highest ever obtained in free‐cell propionic acid fermentation. Biotechnol. Bioeng. 2015;112: 502–511. © 2014 Wiley Periodicals, Inc.
Emission constrained economic dispatch with valve-point effect using particle swarm optimization

This paper presents particle swarm optimization (PSO) technique to solve economic dispatch of valve-point loaded generating units considering emission constraint. This problem has gained recent attention due to the deregulation of power industry and environmental regulations. Minimizing operating cost can no longer be the only criterion for dispatching electric power due to increasing concern over the environmental consideration. In this paper, fuel cost and NOx emission functions are considered and formulated as a single objective optimization problem. Based on the literature survey, it could be found that cost function is taken as a quadratic function and solved for emission economic dispatch. Here, in cost function a sine term is added to model the valve-point effect and then solved using PSO algorithm. The objective function is highly non-linear and the proposed method is validated with IEEE 30-bus system. The results obtained demonstrate the effectiveness of the proposed method for solving the environmental constrained economic dispatch problem.
Ginsenoside Rh2 induces Bcl‐2 family proteins‐mediated apoptosis in vitro and in xenografts in vivo models

The cancer chemoprevention effects of ginseng saponins have been demonstrated against a variety of experimental tumors; however, their molecular mechanisms in vitro and in in vivo models are not well studied. This study was undertaken to gain insights into the molecular mechanisms of ginsenoside Rh2 (Rh2)‐induced cell death in human breast cancer cell lines as well as in in vivo xenografts. Rh2 treatment significantly inhibited viability of both MCF‐7 and MDA‐MB‐231 human breast cells in a concentration‐dependent manner, which correlated with mitochondria‐mediated apoptosis. Rh2‐induced apoptosis was accompanied by the down‐regulation of antiapoptotic proteins Bcl‐2, Bcl‐xL, and Mcl‐1. It also caused induction of the proapoptotic members Bak, Bax, and Bim leading to mitochondrial translocation of Bax and activation of caspases. Moreover, Rh2‐induced apoptosis was partially, yet significantly protected by transient transfection of MCF‐7 cells with Bax‐ and Bak‐targeted siRNAs. Oral gavage of 5 mg Rh2/kg of mouse (three times a week) significantly caused apoptosis of MDA‐MB‐231 xenografts. An increase in Bax and Bak and a decrease in Bcl‐2 and Bcl‐xL transcript levels, in accordance with their protein expression, were observed in tumor tissue. Tumors from Rh2‐treated mice exhibited a markedly higher count of apoptotic bodies and reduced proliferation index compared with control tumors. Our data suggest that Rh2 used in traditional oriental medicine for the treatment of various ailments, may be an attractive agent for the treatment and/or prevention of human breast cancers. J. Cell. Biochem. 112: 330–340, 2011. © 2010 Wiley‐Liss, Inc.
The Relational Context of Social Support: Relationship Satisfaction Moderates the Relations between Enacted Support and Distress

In two studies of kidney transplant patients and their significant others, the authors examined whether the relations between enacted social support and patient distress were moderated by patients' satisfaction with their relationship with the support provider (i.e., their significant other). In Study 1 (n = 121 couples), unsupportive spousal behaviors were associated with more distress only among patients who were less satisfied with their marital relationship. In Study 2 (n = 112 couples), the relations between unsupportive behaviors and distress again varied as a function of the patient's relationship satisfaction, although the particular pattern of the interaction depended on the specific unsupportive behaviors offered to the patient. In both studies, relationship dissatisfaction was associated with higher levels of patient distress. Supportive behaviors were not related to distress and did not interact with relationship satisfaction. Implications for future research on social support in marriage are discussed.
A novel particulate influenza vaccine induces long-term and broad-based immunity in mice after oral immunization

The immunogenicity of a novel particulate oral influenza vaccine was examined in terms of antibody response and protection in mice. Oral immunization with chicken erythrocytes (CRBC) adsorbed with gamma-irradiated influenza A virus induced high levels of immunoglobulin G antibodies and protection in the lung compared with gamma-irradiated virus administered alone or CRBC. Immunoglobulin A antibodies were the predominant antibodies in nasal washings, and their presence did not correlate with protection as well as immunoglobulin G antibodies. Immunity was not specific for the immunizing virus subtype, as antibodies and enhanced lung clearance of virus were demonstrated with different virus subtypes. However, mice were not protected when challenged with live influenza B virus. The antibody response and the degree of protection were dependent on both the concentration of virus adsorbed to CRBC and number of CRBC adsorbed to virus. Virus-adsorbed CRBC given subcutaneously failed to induce antibodies or protection. Oral immunization with A/Qld/6/72 (H3N2) virus gave a high level of protection over 12 weeks, which could be demonstrated with different subtypes. Protection correlated with antibody levels in the lung determined by both enzyme-linked immunosorbent and hemagglutination inhibition assays, although the levels detected by the latter declined over time.
A Clinical Study Comparing Epinephrine 200μg or Clonidine 90μg as Adjuvants to Local Anaesthetic Agent in Brachial Plexus Block Via Supraclavicular Approach

Background: A double blind randomized prospective study was undertaken to determine the effect of adjuncts like epinephrine 200μg or clonidine 90μg in combination of bupivacaine and lignocaine into the brachial plexus sheath to study the sensory and motor onset, duration of analgesia, hemodynamic changes and adverse effects. Patients & Methods: 60 patients aged 18-65 years, with ASA grade I and II were randomly divided into group I and group II to receive 10 ml of lignocaine2% and 20 ml of bupivacaine0.5% with 1ml of 200μg epinephrine or 90μg clonidine respectively. Onset of sensory blockade was determined by pinprick method by a three point score and motor blockade by three point scale. Duration of postoperative analgesia, the hemodynamic changes, sedation scores and any adverse effects were observed. Statistical analysis was done by student's “t” test and p<0.05 was considered significant. Results: It was found that there was faster onset of sensory and motor blockade, the postoperative analgesia was prolonged and the amount of sedation was profound in group II as compared to group I. All the above findings were statistically significant. Conclusion: We thereby conclude that clonidine 90μg is a better option as an additive than epinephrine 200μg for hastening the onset of sensory and motor block with prolonged postoperative analgesia and sedation as the only adverse effect.
A comparison of fresh and cultured T lymphocytes from patients with ataxia telangiectasia using T‐cell subset markers and chromosome translocations

Ataxia telangiectasia (A‐T) is an autosomal recessive disorder in which patients show an unusual predisposition to lymphoid malignancies including T‐cell leukaemia. We compare here the surface phenotypes of fresh and cultured A‐T T cells. A total of 17 T‐cell cultures from 8 A‐T patients are compared with each other and with 5 T‐cell cultures from normal individuals. The large, cytogenetically abnormal t(14;14) and t(X;14) clones in 2 of the patients both occurred only in the CD8 + population of T lymphocytes. There was no difference in the rate of growth of A‐T T cells in vitro compared with those from normal individuals, although many of the original characteristics of the T cells were lost, including the cytogenetically abnormal clones seen in fresh A‐T lymphocytes.
Nuclear Import of Histone Deacetylase 5 by Requisite Nuclear Localization Signal Phosphorylation*

Histone deacetylase 5 (HDAC5), a class IIa deacetylase, is a prominent regulator of cellular and epigenetic processes that underlie the progression of human disease, ranging from cardiac hypertrophy to cancer. Although it is established that phosphorylation mediates 14–3-3 protein binding and provides the essential link between HDAC5 nucleo-cytoplasmic shuttling and transcriptional repression, thus far only four phospho-acceptor sites have been functionally characterized. Here, using a combinatorial proteomics approach and phosphomutant screening, we present the first evidence that HDAC5 has at least 17 in vivo phosphorylation sites within functional domains, including Ser278 and Ser279 within the nuclear localization signal (NLS), Ser1108 within the nuclear export signal, and Ser755 in deacetylase domain. Global and targeted MS/MS analyses of NLS peptides demonstrated the presence of single (Ser278 and Ser279) and double (Ser278/Ser279) phosphorylations. The double S278/279A mutation showed reduced association with HDAC3, slightly decreased deacetylation activity, and significantly increased cytoplasmic localization compared with wild type HDAC5, whereas the S278A and S1108A phosphomutants were not altered. Live cell imaging revealed a deficiency in nuclear import of S278/279A HDAC5. Phosphomutant stable cell lines confirmed the cellular redistribution of NLS mutants and revealed a more pronounced cytoplasmic localization for the single S279A mutant. Proteomic analysis of immunoisolated S278/279A, S279A, and S259/498A mutants linked altered cellular localization to changes in protein interactions. S278/279A and S279A HDAC5 showed reduced association with the NCoR-HDAC3 nuclear corepressor complex as well as protein kinase D enzymes, which were potentiated in the S259/498A mutant. These results provide the first link between phosphorylation outside the known 14–3-3 sites and downstream changes in protein interactions. Together these studies identify Ser279 as a critical phosphorylation within the NLS involved in the nuclear import of HDAC5, providing a regulatory point in nucleo-cytoplasmic shuttling that may be conserved in other class IIa HDACs—HDAC4 and HDAC9.
Mechanical stretching induces osteoprotegerin in differentiating C2C12 precursor cells through noncanonical Wnt Pathways

Mechanical loading is known to be important for maintaining the formation and resorption rates of bone. To study the mechanisms by which mechanical loading regulates osteogenesis, we investigated the role of the Wnt pathway in C2C12 cells committed to osteogenic differentiation in response to cyclic mechanical stretching. Osteoprotegerin (OPG) acts as a decoy receptor for RANKL to inhibit osteoclastogenesis and resorption of bone. Our results demonstrate that stretching leads to a sustained increase in OPG expression in C2C12 cells. The expression of osteogenic marker genes, such as osteocalcin and alkaline phosphatase, was transiently decreased by stretching at 24 hours and returned to control levels at 48 hours. The addition of inhibitors of the canonical Wnt/β‐catenin pathways, such as the secreted FZD‐related peptide sRFP2, as well as siRNA‐mediated knockdown, did not inhibit the effect of stretching on OPG expression. In contrast, treatment with inhibitors of noncanonical Wnt signaling, including KN93, and siRNA for Nemo‐like kinase (NLK) blocked most of the mechanical inductive effect on OPG. Furthermore, stretching‐induced OPG production in the culture medium was able to inhibit the osteoclast formation of bone marrow macrophages. These results suggest that mechanical stretching may play an important role in bone remodeling through the upregulation of OPG and that the mechanical signaling leading to OPG induction involves the noncanonical Wnt pathway. © 2010 American Society for Bone and Mineral Research
By Ounce or by Calorie: The Differential Effects of Alternative Sugar‐Sweetened Beverage Tax Strategies

The obesity epidemic and excessive consumption of sugar-sweetened beverages have led to proposals of economics-based interventions to promote healthy eating in the United States. Targeted food and beverage taxes and subsidies are prominent examples of such potential intervention strategies. This paper examines the differential effects of taxing sugar-sweetened beverages by calories and by ounces on beverage demand. To properly measure the extent of substitution and complementarity between beverage products, we developed a fully modified distance metric model of differentiated product demand that endogenizes the cross-price effects. We illustrated the proposed methodology in a linear approximate almost ideal demand system, although other flexible demand systems can also be used. In the empirical application using supermarket scanner data, the product-level demand model consists of 178 beverage products with combined market share of over 90%. The novel demand model outperformed the conventional distance metric model in non-nested model comparison tests and in terms of the economic significance of model predictions. In the fully modified model, a calorie-based beverage tax was estimated to cost $1.40 less in compensating variation than an ounce-based tax per 3,500 beverage calories reduced. This difference in welfare cost estimates between two tax strategies is more than three times as much as the difference estimated by the conventional distance metric model. If applied to products purchased from all sources, a 0.04-cent per kcal tax on sugar-sweetened beverages is predicted to reduce annual per capita beverage intake by 5,800 kcal.
Longitudinal study on influence of prolonged non-nutritive sucking habits on dental caries in Japanese children from 1.5 to 3 years of age.

The purpose of the present study was to investigate the relationship between infant sucking habits and the prevalence of caries in Japanese preschool children.The study was designed as a prospective, longitudinal study starting with 592 children aged 18 months. Information on sucking habits and patterns of feeding was collected from parents in the form of a questionnaire. Children who continued breastor bottle-feeding at 18 months of age were eliminated prior to the evaluations. The children were divided into 3 groups according to their sucking habits at 18 months of age: Group 1: children with a finger-sucking habit (n=151); Group 2: children who used a pacifier (n=45) and Group 3: children with no oral habit (n=205). Clinical examinations were carried out by one of the authors.Mean dft and prevalence of caries were not statistically significant among the 3 groups at 18 months of age. However, only 10.6% of the children in Group 1 exhibited caries at 36 months of age, compared with 17.1% in Group 3 and 24.4% in Group 2. Group 1 children showed the smallest mean dft at 0.30 among the 3 groups at 36 months of age, and those in Group 2 showed 1.18; the difference was statistically significant (p<0.01). The results suggest that children with a finger-sucking habit are more likely to be free of caries by the age of 3. However, use of pacifier at 18 months of age is a potential risk factor for the development of dental caries in children.
Survival is prolonged by highly active antiretroviral therapy in AIDS patients with primary central nervous system lymphoma

Objective: To determine the effects of highly active antiretroviral therapy (HAART) on survival in AIDS-related primary central nervous system lymphoma (PCNSL). Methods: Survival in consecutive patients with PCNSL at a large county teaching hospital from 1995 to 2001 were analyzed by the log rank test and Cox proportional hazards ratios (HR) were calculated for factors potentially affecting survival. Results: During the study period, 25 patients were diagnosed with PCNSL: 19 definite and 6 probable. At diagnosis, median CD4 cell count was 12 × 106 cells/l (range 1–151) and median HIV viral load was 5.3 log10 copies/ml (range 3.9–5.9). Sixteen patients died (median survival 87 days; range, 0 to > 2112). Longer survival was noted for patients who received HAART after diagnosis [HR for death, 0.06; 95% confidence interval (CI), 0.01–0.48]. Six of seven HAART-treated patients were alive versus 0/18 untreated patients at a median follow-up time of 667 days (P = 0.0007 by log rank test). A survival benefit was seen for patients who had ⩾ 0.5 log10 copies/ml decrease in HIV viral load after diagnosis (n = 6; HR, 0.07; 95% CI, 0.01–0.55) and for patients with a significant CD4 cell rebound (increase ⩾ 50 × 106 cells/l) in response to HAART (n = 6): all survived versus 0/19 survived (P = 0.0003). Cranial radiation therapy (n = 13) prolonged survival (HR, 0.20; 95% CI, 0.07–0.58). Median survival was only 29 days for 11 patients who received neither radiation nor HAART. Conclusions: Receipt of HAART after diagnosis is associated with a significantly longer survival in patients with AIDS-related CNS lymphoma.
A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors.

PURPOSE alpha-galactosylceramide (KRN7000) is a glycosphingolipid that has been shown to inhibit tumor growth and to prolong survival in inoculated mice through activation of natural killer (NK) T cells. We performed a dose escalation study of KRN7000 in advanced cancer patients. EXPERIMENTAL DESIGN Patients with solid tumors received i.v. KRN7000 (50-4,800 micro g/m(2)) on days 1, 8, and 15 of a 4-weekly cycle. Patients were given 1 cycle and, in the absence of dose-limiting toxicity or progression, treatment was continued. Pharmacokinetics (PK) and immunomonitoring were performed in all patients. RESULTS Twenty-four patients were entered into this study. No dose-limiting toxicity was observed over a wide range of doses (50-4,800 micro g/m(2)). PK was linear in the dose range tested. Immunomonitoring demonstrated that NKT cells (CD3+Valpha24+Vbeta11+) typically disappeared from the blood within 24 h of KRN7000 injection. Additional biological effects included increased serum cytokine levels (tumor necrosis factor alpha and granulocyte macrophage colony-stimulating factor) in 5 of 24 patients and a transient decrease in peripheral blood NK cell numbers and cytotoxicity in 7 of 24 patients. Importantly, the observed biological effects depended on pretreatment NKT-cell numbers rather than on the dose of KRN7000. Pretreatment NKT-cell numbers were significantly lower in patients compared with healthy controls (P = 0.0001). No clinical responses were recorded and seven patients experienced stable disease for a median duration of 123 days. CONCLUSION i.v. KRN7000 is well tolerated in cancer patients over a wide range of doses. Biological effects were observed in several patients with relatively high pretreatment NKT-cell numbers. Other therapeutic strategies aiming at reconstitution of the deficient NKT-cell population in cancer patients may be warranted.
Association of Malignancy Prevalence With Test Properties and Performance of the Gene Expression Classifier in Indeterminate Thyroid Nodules

Importance It is crucial for clinicians to know the malignancy prevalence within each indeterminate cytologic category to estimate the performance of the gene expression classifier (GEC). Objective To examine the variability in the performance of the GEC. Design, Setting, and Participants This retrospective cohort study of patients with Bethesda category III and IV thyroid nodules used single-institution data from January 1, 2013, through February 29, 2016. Expected negative predictive value (NPV) was calculated by adopting published sensitivity and specificity. Observed NPV was calculated based on the true-negative rate. Outcomes were compared with pooled data from 11 studies published January 1, 2010, to January 31, 2016. Results A total of 145 patients with 154 thyroid nodules were included in the study (mean [SD] age, 56.0 [16.2] years; 106 females [73.1%]). Malignancy prevalence was 45%. On the basis of this prevalence, the expected NPV is 85% and the observed NPV is 69%. If the prevalence is assumed to be 25%, the expected NPV would be 94%, whereas the observed NPV would be 85%. Pooled data analysis of 11 studies comprising 1303 participants revealed a malignancy prevalence of 31% (95% CI, 29%-34%) and a pooled NPV of 92% (95% CI, 87%-96%). Conclusions and Relevance In this study, variability in the performance of the GEC was not solely a function of malignancy prevalence and may have been attributable to intrinsic variability of the test sensitivity and specificity. The utility of the GEC in practice is elusive because of this variability. A better definition of the GEC’s intrinsic properties is needed.
Changes in health and job attitudes of case managers providing intensive services.

OBJECTIVE The health, personal life, and attitudes of case managers providing intensive services to severely mentally ill clients were evaluated to see how the managers changed over their first 18 months on the job. The authors report here on changes on major variables related to health status and job attitudes. METHODS A cohort of 82 case managers newly hired during the first year of New York State's intensive case management program was followed for 18 months. A battery of measures of health, life events, life satisfaction, social support, job situation, and job attitude was administered by mail questionnaire at job entry and at three, 12, and 18 months to case managers who remained employed in the program. RESULTS Approximately 80 percent of the eligible (still-employed) case managers responded at each time point; 64 were still employed at the end of the study. Over time they experienced increasing amounts of job stress and emotional exhaustion, depersonalized clients more, and reported significantly more stress-related physical symptoms and depressive symptoms. However, their sense of personal accomplishment and their job satisfaction remained stable. CONCLUSIONS Case managers appeared able to overcome job pressures and persevere in their professional commitment. What difficulties they had appeared to level off after one year, at least among those who continued in their positions. Although the findings do not indicate that case managers need intensive help, early support and preventive intervention for job difficulties would be helpful.