Miracle-dz/UniFAR-FTUs huggingface dataset:
Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

Abstract. The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.
Temporal declines in tree longevity associated with faster lifetime growth rates in boreal forests

Global change has been linked to significant increases in tree mortality in the world’s forests. Reduced tree longevity through increased growth rates has been suggested as one of the mechanisms responsible for the temporal increases in tree mortality, but this idea has not been directly tested. Here we explicitly defined two testable hypotheses: (i) the probability of ageing driven tree mortality increases with global change and (ii) the mortality probability associated with global change is higher for faster growing trees. To test these hypotheses, we examined the temporal changes of tree mortality probability in 539 permanent sample plots monitored from 1960–2009, with ages greater than 100 years at initial censuses, across the boreal region of Alberta, Canada. As expected, we found an overall temporal increase in tree mortality probability, indicating a loss in tree longevity with global change. We also found that trees with faster lifetime growth rates experienced higher temporal increases in mortality probability compared to slower growing trees. An analysis of the responses of tree mortality probability to increasing atmospheric carbon dioxide and temperature and decreases in water availability indicated that increasing atmospheric carbon dioxide and decreasing water availability were the major drivers of declining longevity. Our results suggest that tree longevity may further decline with the expected increase of atmospheric carbon dioxide and decreasing water availability in the region.
Prevalence of subclinical ketosis in mainly pasture-grazed dairy cows in New Zealand in early lactation

AIMS: The main aim of this study was to describe the prevalence of primary subclinical ketosis (SCK) in mainly pasture-grazed dairy cows in three dairy-farming regions of New Zealand 7–12, and 35–40 days post-calving. A second aim was to investigate herd- and cow-level factors associated with the prevalence of SCK. METHODS: A cross-sectional longitudinal prevalence survey was undertaken in 1,620 dairy cows from 57 herds. A random sample of cows without disease in the prior 30 days were enrolled at one farm visit within 5 days of calving, and blood samples were collected 7 and 28 days later (7–12 and 35–40 days post-calving) for measurement of beta-hydroxy butyrate (BHBA) concentrations using an electronic cow-side meter. SCK was defined as blood BHBA concentration ≥1.4 mmol/L. RESULTS: Mean cow-level prevalence of SCK varied with interval post-calving (16.8 and 3.2% at 7–12 days and 35–40 days post-calving, respectively) and age (13.0 and 13.1% of 2-year olds and ≥8-year olds, respectively, compared to 7.2% of 3–4-year-old cows). Mean herd-level prevalence of SCK was 14.3 (min 0, max 60.0)% and 2.6 (min 0, max 24.4)% at 7–12 days and 35–40 days post-calving, respectively, and was greater in Southland (13.3%) than Waikato and Canterbury herds (6.9 and 4.7%, respectively). CONCLUSIONS: This is the first population-based report of the prevalence of SCK in New Zealand dairy herds and demonstrates that age and interval post-calving are important risk factors determining prevalence; and that there is wide variation in prevalence between herds. CLINICAL RELEVANCE: Subclinical ketosis may be unrecognised but common in many New Zealand dairy cows in the first 2 weeks of lactation.
The Impact of Tourism on the Local Economy in Malaysia

The local and international communities play an important role in the sustainable growth of the Malaysian tourism industry. The principle of sustainable growth in the tourism industry was proposed by the World Tourism Organization (WTO) in 1988. As the tourism industry is one of the largest and fastest growing industries in Malaysia, the government has poured considerable effort into promoting this industry consistent with the objective of the Economic Transformation Program (ETP) to transform from a resource-based economy to a service-based economy. This study aimed to test the hypothesis of tourism-led growth from Malaysia’s perspective. The tourism revenue earned by the government can be used to invest in industry to further promote economic growth in Malaysia. Hence, tourist receipts and capital investment in the tourism industry are important factors that can affect the nation’s economic growth. Utilizing Malaysian data from 1995 to 2016, the study employed the Autoregressive Distributed Lag (ARDL) approach to examine whether the tourism-led growth is valid in this study. Empirical findings indicated that both variables have a significant positive impact on economic growth and the hypothesis of tourism-led growth is accepted in Malaysia.
Peroxynitrite Is an Essential Component of Cytokines Production Mechanism in Human Monocytes through Modulation of Nuclear Factor-κB DNA Binding Activity*

The mechanism of release of proinflammatory cytokines by peripheral blood monocytes is unknown. Peroxynitrite (ONOO−) formed by the reaction of nitric oxide (NO) and superoxide is released predominantly by inflammatory cells at the site of injury in several inflammatory pathologies. Here we show that human monocytes treated with ONOO− at micromolar concentrations induce a dose-dependent release of proinflammatory cytokines. These effects were not antagonized by up to 100 μmepigallocatechin gallate, an inhibitor of protein nitration. However, the proteasome inhibitor Z-Ile-Glu(OtBu)-Ala-Leu-CHO and 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride, a cell-permeable scavenger of ONOO−, almost completely inhibited the release of cytokines and the nuclear translocation of the nuclear factor (NF)-κB transcription factor. SDS-PAGE electrophoresis separation with Western blotting of cell extracts also indicated that phosphorylation and nitration of tyrosine residues in IκB-α molecules correlated with NF-κB translocation and cytokine release. In addition, the DNA binding activity of the NF-κB from the nuclear extracts also correlated with its nuclear translocation. These findings indicate ONOO− plays an essential role in the mechanism of proinflammatory cytokine release by monocytes and that Rel/NF-κB activation is the obligatory pathway.
Resting-State Functional Connectivity of the Subthalamic Nucleus to Limbic, Associative, and Motor Networks

The subthalamic nucleus (STN) is a small structure situated deep in the midbrain that exhibits wide-ranging functionality. In addition to its role in motor control, the STN is considered a hub for synchronizing aspects of emotion and cognition including attention, inhibitory control, motivation, and working memory. Evidence from neuroanatomical tracer studies suggests that the medial, ventromedial, and dorsolateral parts of the STN correspond to limbic, associative, and motor subdivisions, respectively. Although the extent of STN functional anatomical overlap remains unclear, blood oxygenation level dependent imaging of the STN may provide complementary information about the diverse functions of this structure. Methodological limitations in spatial and temporal resolutions, however, have prevented a comprehensive exploration of temporal correlations from the STN to the whole brain. In this study, we optimize spatial (2 mm isotropic) and temporal (TR = 1 s) resolutions to take full advantage of the time series signal-to-noise ratio capabilities of multichannel array coils and simultaneous multislice imaging. We interrogated STN seed-to-voxel resting-state functional MRI connectivity in a group of 30 healthy participants that included the whole brain at high-temporal and spatial resolutions. This analysis revealed STN functional connectivity to limbic, associative, and motor networks. Our findings contribute to the understanding of STN functional neuroanatomy in humans and are clinically relevant for ongoing research in deep brain stimulation.
Factors influencing the successful treatment of infectious pulmonary tuberculosis.

SETTING Achieving successful treatment of infectious pulmonary tuberculosis (PTB) could reduce the spread of tuberculosis (TB) and the emergence of multidrug resistance. OBJECTIVE To explore factors associated with successful treatment for sputum-positive PTB. DESIGN This study used a population-based retrospective cohort design. All PTB patients residing in southern Taiwan recorded in the tuberculosis registry from 1 January to 30 June 2003 were identified. Each patient's medical record was requested from treating hospitals and retrospectively reviewed for 15 months after the date PTB was confirmed. RESULTS There were 399 PTB patients included in the study. Factors significantly associated with successful treatment included treatment by pulmonologists (OR 1.93), receiving directly observed therapy (DOT) (OR 1.76) and receiving treatment at the chest hospital (OR 5.41). Patients of advanced age were less likely to achieve treatment success (OR 0.97). Among patients treated by pulmonologists, those treated at the chest hospital had a significantly higher treatment success rate than those treated at other institutions (94.1% vs. 69.9%). CONCLUSIONS Patients treated with DOT and by pulmonologists, especially at the chest hospital, had a higher treatment success rate. DOT and training of care professionals and institutions are therefore important factors that affect the successful treatment of TB.
The Cytochrome bc 1 and Cytochromec Oxidase Complexes Associate to Form a Single Supracomplex in Yeast Mitochondria*

The mitochondrial electron transport chain complexes are large multisubunit complexes embedded in the inner membrane. We report here that in the yeast Saccharomyces cerevisiae, the cytochrome bc 1 and cytochrome c oxidase complexes co-exist as a larger complex of ∼1000 kDa in the mitochondrial membrane. Following solubilization with a mild detergent, the cytochromebc 1-cytochrome c oxidase complex remains stable. It was analyzed using the techniques of gel filtration and blue native-polyacrylamide gel electrophoresis. Direct physical association of subunits of the cytochrome bc 1complex with those of the cytochrome c oxidase complex was verified by co-immunoprecipitation analysis. Our data indicate that the cytochrome bc 1 complex is exclusively in association with the cytochrome c oxidase complex in yeast mitochondria. We term this complex the cytochromebc 1-cytochrome c oxidase supracomplex.
The impact of firm characteristics on speed of adjustment to target leverage: a UK study

ABSTRACT Responding to the need to investigate heterogeneity in the speed of adjustment (SOA) to target leverage in a manner that reflects the fractional nature of leverage, we estimate SOA across sub-samples of UK firms using the Dynamic Panel Fractional (DPF) estimator. Using firm characteristics to identify firms subject to varying costs of deviation from and adjustment to target leverage, we find significant evidence of heterogeneity in the speeds at which UK firms adjust to target leverage. Our results show that small, high growth and low dividend paying firms adjust to target leverage faster than their large, low growth and high dividend paying counterparts. We also find some evidence to suggest openly held firms adjust faster than closely held firms, though our results are not robust to the categorizing criterion employed or target leverage specification.
Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA

The transition from ductal carcinoma in situ to invasive ductal carcinoma is a key event in breast cancer progression that is still not well understood. To discover the microRNAs regulating this critical transition, we used 80 biopsies from invasive ductal carcinoma, 8 from ductal carcinoma in situ, and 6 from normal breast. We selected them from a recently published deep-sequencing dataset [Farazi TA, et al. (2011) Cancer Res 71:4443–4453]. The microRNA profile established for the normal breast to ductal carcinoma in situ transition was largely maintained in the in situ to invasive ductal carcinoma transition. Nevertheless, a nine-microRNA signature was identified that differentiated invasive from in situ carcinoma. Specifically, let-7d, miR-210, and -221 were down-regulated in the in situ and up-regulated in the invasive transition, thus featuring an expression reversal along the cancer progression path. Additionally, we identified microRNAs for overall survival and time to metastasis. Five noncoding genes were associated with both prognostic signatures—miR-210, -21, -106b*, -197, and let-7i, with miR-210 the only one also involved in the invasive transition. To pinpoint critical cellular functions affected in the invasive transition, we identified the protein coding genes with inversely related profiles to miR-210: BRCA1, FANCD, FANCF, PARP1, E-cadherin, and Rb1 were all activated in the in situ and down-regulated in the invasive carcinoma. Additionally, we detected differential splicing isoforms with special features, including a truncated EGFR lacking the kinase domain and overexpressed only in ductal carcinoma in situ.
Exploring Mispricing in the Term Structure of CDS Spreads

Based on a reduced-form model of credit risk, we explore mispricing in the credit default swaps (CDS) spreads of North American companies and its economic content. Specifically, we develop a trading strategy using the model to trade out of sample market-neutral portfolios across the term structure of CDS contracts. Our empirical results show that the trading strategy exhibits abnormally large returns, confirming the existence and persistence of a mispricing. The aggregate returns of the trading strategy are positively related to the square of market-wide credit and liquidity risks, indicating that the mispricing is more pronounced when the market is more volatile. When implemented on the Markit data, the strategy shows significant economic value even after controlling for realistic transaction costs.
PspA and PspC Minimize Immune Adherence and Transfer of Pneumococci from Erythrocytes to Macrophages through Their Effects on Complement Activation

ABSTRACT Pneumococcal surface protein A (PspA) and PspC are important virulence factors. Their absence has been shown to allow improved clearance of pneumococci from the blood of mice and to decrease pneumococcal virulence. In the presence of antibody and complement, pneumococci attach to erythrocytes in a process called immune adherence (IA), which facilitates their delivery to, and eventual phagocytosis by, macrophages. It is not known, however, if PspA and PspC affect IA. Using PspA and/or PspC isogenic mutants and complement-deficient mouse sera, we demonstrated that absence of PspA allows greater deposition of C1q and thus increased classical-pathway-mediated C3 deposition. In the absence of both PspA and PspC, there is also a major increase in C1q-independent C3 deposition through the alternative pathway. The latter was observed even though absence of PspC alone did not have a major effect on alternative-pathway-dependent complement deposition. The enhanced complement C3 deposition realized in the absence of PspA alone and in the absence of PspA and PspC resulted in both greatly increased IA to human erythrocytes and improved transfer of pneumococci from erythrocytes to phagocytes. These data provide new insight into how PspA and PspC act in synergy to protect pneumococci from complement-dependent clearance during invasive infection.
Dietary intake and body composition of football players during the holy month of Ramadan

Abstract Healthy young male football players who were either fasting (n = 59) or not fasting (n = 36) during the month of Ramadan were studied. Body mass, body composition, and dietary intake were assessed at each time point. Energy intake was relatively stable in the fasting participants, but there was a small decrease of approximately 0.7 kg in body mass during Ramadan. Mean daily energy intake increased from 14.8 MJ (s = 2.9) to 18.1 MJ (s = 3.2) during Ramadan in non-fasting participants, with concomitant increases in body mass and body fat content of about 1.4 kg and 1% respectively over the month. The fractional intake of protein increased and the fractional contribution of carbohydrate decreased for both groups in Ramadan. Estimated mean daily water intake was high (about 3.8 litres) throughout the study period. Water intake increased on average by 1.3 litres · day−1 in line with the greater energy intake in the non-fasting group in Ramadan. Daily sodium intake fell during Ramadan in the fasting participants from 5.4 g (s = 1.1) before Ramadan to 4.3 g (s = 1.0) during Ramadan, but increased slightly by about 0.7 g · day−1 in the non-fasting group. Dietary iron decreased in the fasting group and increased in the non-fasting group, reflecting the difference in energy intake in both groups during Ramadan. These data suggest that Ramadan fasting had some effects on diet composition, but the effects were generally small even though the pattern of eating was very different. After Ramadan, the dietary variables reverted to the pre-Ramadan values.
Properties of the LP-805-induced potassium currents in cultured bovine pulmonary artery endothelial cells.

The actions of 8-tert-butyl-6,7-dihydropyrolo[3,2-e]-5- methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (LP-805) on membrane K+ currents in cultured bovine pulmonary artery endothelial cells were investigated using the patch-clamp technique. In the whole-cell voltage clamp experiments, with 11 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the pipette, membrane currents revealed only an inwardly rectifying K+ current, and no outward current could be observed at depolarized potentials. Using a pipette solution containing 0.3 mM EGTA, outward K+ current was present in response to depolarizing voltage steps from a holding potential of -60 mV. LP-805 (1-10 microM) significantly increased outward K+ currents in a concentration-dependent manner. The increase of this K+ current was inhibited by 5 mM tetraethylammonium and 5 mM tetrabutylammonium to a level less than the control. Partial recovery occurred on washout. However, the increase of outward K+ current by 10 microM LP-805 was unaffected by 5 mM 4-aminopyridine and 1 microM glibenclamide. LP-805 (1-10 microM) significantly decreased the inwardly rectifying K+ current in a concentration-dependent manner. In cell-attached patches, inward single K+ currents were recorded at negative membrane potentials, and single channel conductance was 23 +/- 2 pS (n = 5). No outward current could be observed at positive potentials. LP-805 (10 microM) inhibited the inwardly rectifying K+ currents. Thus LP-805 inhibits inwardly rectifying K+ currents but activates outward Ca(++)-dependent K+ currents in bovine pulmonary artery endothelial cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Age-related nuclear lens opacities are associated with reduced growth before 1 year of age.

PURPOSE The aim of this study was to assess the relationship between fetal and infant growth, as measured by birthweight and weight at 1 year and the development of age-related lens opacities. METHODS A total of 1428 men and women who were born in Hertfordshire, United Kingdom, between 1920 and 1930, and for whom records of birthweight and weight at 1 year were available, were traced and invited for examination. Of these, 717 (50%) attended for ophthalmic examination. After dilation with tropicamide 1%, lens opacities were graded using the Lens Opacities Classification System (LOCS) III. RESULTS In this population of English men and women aged 64 to 74 years, most opacities were of the nuclear type. There was no association between birthweight and nuclear lens opacities. Weight at 1 year was negatively correlated with nuclear opacity score in adult life (P=0.001). Subjects in the highest tertile for weight at 1 year (>23 pounds) had an odds ratio of 0.35 (95% confidence interval, 0.17 to 0.74) for having a significant nuclear lens opacity (LOCS score of > or = 3) compared with people in the lowest tertile for weight at 1 year (<21 pounds). This association remained after controlling for age, sex, smoking, social class, adult height, and diabetes. CONCLUSIONS To our knowledge, this is the first time that such an association has been reported; it needs to be replicated in other populations. It could provide part of the explanation for the observed excess risk of cataract in developing countries.
Atypical Glandular Cells: New Bethesda Terminology and Management Guidelines

Although Pap tests have enabled early detection of premalignant lesions, the introduction of new collecting devices has significantly improved the detection of lesions hidden in the endocervical canal, such as adenocarcinoma in situ (AIS). The term “atypical glandular cells of undetermined significance” (AGUS) was introduced at the 1988 Bethesda Conference and defined as morphologic changes in glandular cells beyond those that are suggestive of the benign reactive process, but insufficient for the diagnosis of adenocarcinoma in situ (AIS). In the new 2001 Bethesda System, the term has been eliminated and replaced with the term “atypical glandular cells” (AGC), with the following subclassifications: not otherwise specified (NOS), favor neoplasia, endocervical AIS, and adenocarcinoma. The risks of premalignant or malignant disease associated with the AGC favor neoplasia category are substantially higher than in the AGC NOS category (96% vs. 9–41%, respectively). Patients diagnosed with AGC NOS or AGC favor neoplasia will require colposcopy, endocervical sampling, and, for patients over 35 years of age, endometrial biopsy. If all of these tests are negative, the Pap test should be repeated in 4–6 month intervals until 4 consecutive normal tests are obtained. Positive results in one of the tests will require management according to ASCCP guidelines. The AGC favor neoplasia diagnosis also requires cervical conization and/or other testing, as the incidence of premalignant or malignant lesions in patients with this diagnosis is high. The role of HPV testing in this setting is unknown at this time. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to outline the new Bethesda terminology and management guidelines and list the best devices for obtaining a Pap test.