Miracle-dz/UniFAR-FTUs huggingface dataset:
Eight-Color Multiplex Immunohistochemistry for Simultaneous Detection of Multiple Immune Checkpoint Molecules within the Tumor Microenvironment

Therapies targeting immune checkpoint molecules CTLA-4 and PD-1/PD-L1 have advanced the field of cancer immunotherapy. New mAbs targeting different immune checkpoint molecules, such as TIM3, CD27, and OX40, are being developed and tested in clinical trials. To make educated decisions and design new combination treatment strategies, it is vital to learn more about coexpression of both inhibitory and stimulatory immune checkpoints on individual cells within the tumor microenvironment. Recent advances in multiple immunolabeling and multispectral imaging have enabled simultaneous analysis of more than three markers within a single formalin-fixed paraffin-embedded tissue section, with accurate cell discrimination and spatial information. However, multiplex immunohistochemistry with a maximized number of markers presents multiple difficulties. These include the primary Ab concentrations and order within the multiplex panel, which are of major importance for the staining result. In this article, we report on the development, optimization, and application of an eight-color multiplex immunohistochemistry panel, consisting of PD-1, PD-L1, OX40, CD27, TIM3, CD3, a tumor marker, and DAPI. This multiplex panel allows for simultaneous quantification of five different immune checkpoint molecules on individual cells within different tumor types. This analysis revealed major differences in the immune checkpoint expression patterns across tumor types and individual tumor samples. This method could ultimately, by characterizing the tumor microenvironment of patients who have been treated with different immune checkpoint modulators, form the rationale for the design of immune checkpoint-based immunotherapy in the future.
A view of early vertebrate evolution inferred from the phylogeny of polystome parasites (Monogenea: Polystomatidae)

The Polystomatidae is the only family within the Monogenea to parasitize sarcopterygians such as the Australian lungfish Neoceratodus poisteri and freshwater tetrapods (lissamphibians and chelonians). We present a phylogeny based on partial 18S rDNA sequences of 26 species of Polystomatidae and three taxon from the infrasubclass Oligonchoinea (= Polyopisthocotylea) obtained from the gills of teleost fishes. The basal position of the polystome from lungfish within the Polystomatidae suggests that the family arose during the evolutionary transition between actinopterygians and sarcopterygians, ca. 425 million years (Myr) ago. The monophyly of the polystomatid lineages from chelonian and lissamphibian hosts, in addition to estimates of the divergence times, indicate that polystomatids from turtles radiated ca. 191 Myr ago, following a switch from an aquatic amniote presumed to be extinct to turtles, which diversified in the Upper Triassic. Within polystomatids from lissamphibians, we observe a polytomy of four lineages, namely caudatan, neobatrachian, pelobatid and pipid polystomatid lineages, which occurred ca. 246 Myr ago according to molecular divergence–time estimates. This suggests that the first polystomatids of amphibians originated during the evolution and diversification of lissamphibian orders and suborders ca. 250 Myr ago. Finally, we report a vicariance event between two major groups of neobatrachian polystomes, which is probably linked to the separation of South America from Africa ca. 100 Myr ago.
- 1-Fully Modified HP Filter

Business cycle estimation is core of macroeconomics research. Hodrick-Prescott (1997) filter, (or HP filter), is the most popular tool to extract cycle from a macroeconomic time series. There are certain issues with HP filter including fixed value of λ across the series/countries and end points bias (EPB). Modified HP filter (MHP) of McDermott (1997) attempted to address the first issue. Bloechl (2014) introduced a loss function minimization approach to address the EPB issue but keeping lambda fixed (as in HP filter). In this study we marry the endogenous lambda approach of McDermott (1997) with loss function minimization approach of Bloechl (2014) to analyze EPB in HP filter, while intuitively changing the weighting scheme used in the latter. We contribute by suggesting an endogenous weighting scheme along with endogenous smoothing parameter to resolve EPB issue of HP filter. We call this fully modified HP (FMHP) filter. Our FMHP filter outperforms a variety of conventional filters in a power comparison (simulation) study as well as in observed real data (univariate and multivariate) analytics for a large set of countries.
Persistent Chromatin Modifications Induced by High Fat Diet*♦

Obesity is a highly heritable complex disease that results from the interaction of multiple genetic and environmental factors. Formerly obese individuals are susceptible to metabolic disorders later in life, even after lifestyle changes are made to mitigate the obese state. This is reminiscent of the metabolic memory phenomenon originally observed for persistent complications in diabetic patients, despite subsequent glycemic control. Epigenetic modifications represent a potential mediator of this observed memory. We previously demonstrated that a high fat diet leads to changes in chromatin accessibility in the mouse liver. The regions of greatest chromatin changes in accessibility are largely strain-dependent, indicating a genetic component in diet-induced chromatin alterations. We have now examined the persistence of diet-induced chromatin accessibility changes upon diet reversal in two strains of mice. We find that a substantial fraction of loci that undergo chromatin accessibility changes with a high fat diet remains in the remodeled state after diet reversal in C57BL/6J mice. In contrast, the vast majority of diet-induced chromatin accessibility changes in A/J mice are transient. Our data also indicate that the persistent chromatin accessibility changes observed in C57BL/6J mice are associated with specific transcription factors and histone post-translational modifications. The persistent loci identified here are likely to be contributing to the overall phenotype and are attractive targets for therapeutic intervention.
Are Arbitrators Political ? Evidence from International Investment Arbitration

This paper examines the role of arbitrator background for outcomes in arbitration between foreign investors and the host states. We construct a unique personnel data set of more than 500 arbitrators who have been appointed to adjudicate investment disputes before the International Centre for the Settlement of Investment Disputes (ICSID). Among presiding arbitrators appointed by ICSID and arbitrators whose votes are revealed, we nd that the tribunal decisions are weakly correlated with an external measure of legal strength but strongly correlated with arbitratorspolicy preferences. When the presiding arbitratorspolicy preferences are closer to those of the arbitrators one party frequently appoints, the tribunal decisions bias toward that party. Among the bias factors, an arbitrators developing status is most prominent. We also show that a standing tribunal may give greater room for arbitrators to bring their policy preferences to bear on disputes before them. We thank Stefan Bechtold, Markus Burgstaller, David Caron, Mark Clotfelter, James Crawford, Chris Crowe, Rudolf Dolzer, Zachary Douglas, Jack Goldsmith, Thomas C. Grant, Luis Gonzalez Garcia, Susan Franck, Luis Garicano, Gerard Hertig, Luis Kaplow, Jan Kleinheisterkamp, Andrew Lang, Katerina Linos, Federico Ortino, William W. Park, Lauge Poulsen, Dan Price, Todd Rako¤, Lucy Reed, Anthea Roberts, Evgeniya Rubinina, Philippe Sands, Christoph Schreuer, Beth Simmons, Alejandro Turyn, Albert Jan van den Berg, Pierre-Hughes Verdier, Guglielmo Verdirame and David Williams for discussions and comments. In addition, we are grateful to many lawyers working in investment arbitration who shared information that enabled us to construct our dataset. We presented earlier versions of this paper at Berkeley, BIICL, Bonn, Buenos Aires, ETH, LSE, Santa Clara, Virginia, UCLA and USC. Devika Agarwal, Radhika Agarwal, Christina Gort, Florence Hediger, Cedric Mercken, Margaux Salmon, Bhushan Satish and Leah Wald assisted in collecting data. yMichael Waibel is University Senior Lecturer, and Co-Deputy Director of the Lauterpacht Centre for International Law, University of Cambridge. zYanhui Wu is Assistant Professor at the USC Marshall School of Business.
The effects of metabolic inhibition and acidification on force production in the rat uterus

The effects of hypoxia and intracellular acidification were examined on the mechanical properties of the non‐pregnant and pregnant rat uterus. Isolated uteri were investigated during control conditions and in the presence of cyanide, to simulate hypoxia or the salts of weak acids and bases to change intracellular pH at constant external pH (pH 7.4). Both spontaneous contractions and high‐K contractures (i.e. fully activated preparations) were investigated at 37 degrees C. In control solutions both pregnant and non‐pregnant uteri were spontaneously active and gave a contracture when bathed with a high‐K+ solution. When oxidative phosphorylation was inhibited by cyanide, spontaneous contractions were either greatly reduced or abolished. The effects on spontaneous contractions were more pronounced in the non‐pregnant than the pregnant uterus. If high‐K solution was added after cyanide had abolished spontaneous contractions, then a small amount of force was produced. High‐K‐induced contractures were not maintained in the presence of cyanide and quickly fell to baseline levels in both pregnant and non‐pregnant uteri. All the effects of cyanide were fully reversible. When only intracellular pH was changed by adding weak acids (50 mM‐butyrate or propionate), spontaneous contractions were greatly diminished or abolished in both pregnant and non‐pregnant uteri. However, the application of weak acids had no effect upon the KCl‐induced contractures in both pregnant and non‐pregnant uteri. The effects of cyanide on the uterus include both an acidification and changes in metabolites, e.g. a fall in [ATP]. To investigate the changes in metabolites without a change in pHi, cyanide was applied with the weak base trimethylamine (40–50 mM). 31P Nuclear magnetic resonance spectroscopy was used to show that the alkalinization which occurs with trimethylamine alone abolished the acidification ordinarily associated with cyanide. Spontaneous and high‐K‐induced contractions were greatly reduced or abolished, i.e. the result was the same as with cyanide alone. This occurred in both pregnant and non‐pregnant uteri. It is concluded that spontaneous force production is affected by both changes in metabolites (e.g. decreased [ATP] and increased inorganic phosphate) and pHi, and that both can depress activation of the uterus. Only the changes in metabolites can depress force production in fully activated preparation. The greater effect on force in the non‐pregnant uterus compared to the pregnant uterus may be due to the lower initial levels of [ATP] and the greater fall in ATP seen in non‐pregnant compared to pregnant uterus, and gestational changes in metabolism. (ABSTRACT TRUNCATED AT 400 WORDS)
Behavioral and psychosocial profiles of alcohol-exposed children.

BACKGROUND It is widely known that prenatal alcohol exposure is related to cognitive and behavioral deficits throughout childhood and adolescence. Much research has focused on understanding and quantifying the cognitive profile of children with fetal alcohol syndrome (FAS) with relatively less empirical research on behavioral or psychosocial adjustment. The primary purpose of this study was to examine the behavioral and psychosocial profile of children exposed to heavy amounts of alcohol prenatally. METHOD Two groups of subjects were evaluated: an alcohol-exposed group (ALC) and a nonexposed control group (NC) each made up of 32 subjects matched for age, gender, and ethnicity. The alcohol-exposed group consisted of children heavily exposed to alcohol in utero, including 19 children diagnosed with FAS. The Personality Inventory for Children (PIC) was completed by the caretaker of each child. Four validity/screening scales and 12 clinical scales were scored for all subjects. RESULTS Analyses revealed significant group differences on four validity/screening scales and 12 substantive scales. Within the ALC group, the profile of children without FAS was similar to that of children with FAS, with the exception that their profiles were consistent with less cognitive impairment. CONCLUSIONS These findings indicate that in addition to previously reported cognitive impairments, heavy prenatal alcohol exposure is related to significant impairments in psychosocial functioning. Even children without alcohol-related physical anomalies suffer from impaired psychosocial functioning. Because impairments of this nature can interfere with functioning across multiple domains, effective early intervention programs should be considered for families of alcohol-exposed children. Furthermore, given the similarities of alcohol-exposed children with and without FAS, it is imperative to obtain prenatal alcohol exposure histories on all children experiencing cognitive or psychosocial deficits.
Ground Improvement Using Displacement Type Sand Piles

Stone columns are widely adopted to improve weak/loose ground to achieve adequate bearing capacity. Displacement type stone column /granular piles can densify loose sand/silty sand and strengthen the ground. In present a laboratory investigation has been made to investigate the improvement on the ultimate bearing capacity due to installation of a group of displacement type granular piles on loose sand bed. Effect of improving the surrounding region of the footing on the Ultimate bearing capacity has also been examined. Ultimate bearing capacity has been computed from Plate load tests results conducted on loose sand bed and also on improved sand bed. Two types of material sand itself and gravelly sand were used as granular pile material. Comparison has also been made between the two types of materials used in stone column in term of load carrying capacity. A method also suggested for estimating the ultimate bearing capacity of the stone column improved ground which is supported by experimental result.
Screening and development of resistant sesame varieties against phytoplasma

Initially 150 germplasm, 32 released varieties and 4 wild spp. of sesame were evaluated under field conditions during Kharif-2005 and promising lines selected under artificial conditions during subsequent two seasons. Three intraand two interspecific crosses were selected to study the inheritance of phyllody resistance in sesame whereas, two each of intraand interspecific crosses were identified to test the allelic relationship between resistant genes. The F2 and backcross segregation analysis in intraspecific crosses revealed that a single recessive gene governs phyllody resistance whereas that of interspecific combinations suggested the involvement of a single dominant gene. Allelic test on intraspecific crosses revealed recessive resistance to be governed by two independent non-allelic genes exhibiting duplicate dominance whereas, interspecific crosses showed the dominance nature of resistance with the involvement of one dominant and one recessive gene.
Position effects influencing intrachromosomal repair of a double-strand break in budding yeast

Repair of a double-strand break (DSB) by an ectopic homologous donor sequence is subject to the three-dimensional arrangement of chromosomes in the nucleus of haploid budding yeast. The data for interchromosomal recombination suggest that searching for homology is accomplished by a random collision process, strongly influenced by the contact probability of the donor and recipient sequences. Here we explore how recombination occurs on the same chromosome and whether there are additional constraints imposed on repair. Specifically, we examined how intrachromosomal repair is affected by the location of the donor sequence along the 812-kb chromosome 2 (Chr2), with a site-specific DSB created on the right arm (position 625kb). Repair correlates well with contact frequencies determined by chromosome conformation capture-based studies (r = 0.85). Moreover, there is a profound constraint imposed by the anchoring of the centromere (CEN2, position 238kb) to the spindle pole body. Sequences at the same distance on either side of CEN2 are equivalently constrained in recombining with a DSB located more distally on one arm, suggesting that sequences on the opposite arm from the DSB are not otherwise constrained in their interaction with the DSB. The centromere constraint can be partially relieved by inducing transcription through the centromere to inactivate CEN2 tethering. In diploid cells, repair of a DSB via its allelic donor is strongly influenced by the presence and the position of an ectopic intrachromosomal donor. Author Summary A double-strand break (DSB) on a chromosome can be repaired by recombining with an ectopic homologous donor sequence. Interchromosomal ectopic recombination is strongly influenced by the three-dimensional arrangement of chromosomes in the nucleus of haploid budding yeast, that is strongly influenced by the probability of chemical cross-linking of the donor and recipient sequences. Here we explore how recombination occurs on the same chromosome. We examined how intrachromosomal repair is affected by the location of the donor sequence along the 812-kb chromosome 2 (Chr2), with a site-specific DSB created on the right arm (position 625kb). Repair correlates well with contact frequencies determined by chromosome conformation capture-based studies (r = 0.85). Moreover, there is a profound constraint imposed by the anchoring of the centromere (CEN2, position 238kb) to the spindle pole body. Sequences at the same distance on either side of CEN2 are equivalently accessible in recombining with a DSB located more distally on one arm, suggesting that sequences on the opposite arm from the DSB are not otherwise constrained in their interaction with the DSB. The centromere constraint can be partially relieved by inducing transcription through the centromere to inactivate CEN2 tethering. In diploid cells, repair of a DSB via its allelic donor is strongly influenced by the presence and the position of an ectopic intrachromosomal donor.
Effect of Cooling Rate on ( ε , α ’ ) Martensite Formation in Twinning / transformation-induced Plasticity Fe – 17 Mn – 0 . 06 C Steel

The cooling rate, density of stacking faults, austenite grain size, and temperature strongly influence the γfcc → εhcp → α’bcc martensite transformation in austenitic alloys. During cooling, austenitic Fe–Mn steels can partially transform to ε and α’ martensites within a restricted chemical composition. Martensite formation will influence the mechanical behavior of the alloy. The microstructure evolution under three cooling rates of a hot-rolled austenitic steel, Fe–17.0Mn–0.06C (wt%), was analyzed by optical microscopy and scanning electron microscopy/electron backscatter diffraction. The volume fraction of martensite and austenite were measured by X-ray diffraction line profile analysis by directly comparing the as-cast alloy, alloy subjected to different cooling conditions, and this processed with hot rolling.
EFFECT OF SPACING ON GROWTH , FLOWER YIELD AND QUALITY OF CALENDULA UNDER VIDARBHA ( M . S . ) CONDITIONS

An experiment entitled “Effect of spacing on growth, flower yield and quality of calendula” was carried out at Horticulture Section, College of Agriculture, Nagpur (M.S.), India during the year 2011-12 with seven treatments of spacing viz., 30x30 cm, 30x20 cm, 30x10 cm, 20x20 cm, 20x10 cm, 15x15 cm and 15x10 cm in randomized block design. The results revealed that, the wider spacing of 30x30 cm recorded significantly maximum branches plant -1 , leaf area, flowering span, cut flower yield plant -1 and thickness of flower stalk, whereas, closer spacing 15x10 cm recorded maximum height of plant, stalk length of flower and minimum days to first flower bud initiation and flower opening from bud initiation. (
PERSISTENT OVERCONFIDENCE: EVIDENCE FROM A FIELD EXPERIMENT IN UGANDA

In this paper, I study persistency of overconfidence. I bring evidence from a largescale field experiment (N=5,102) on whether providing detailed repeated feedback to students evaluated in groups in different types of tournaments helps them predict their performance more accurately. Students in the experiment are overly overconfident and group feedback only helps them offset their inflated beliefs created by task repetition. Feedback exhibits diminishing returns to information. Improving self-assessment is associated with higher performance but lower happiness. Finally, inability to accurately assess own performance may serve as an additional channel to explain gender differences in Math performance.
Heritability , variability and genetic advance analysis for yield contributing characters in rice ( Oryza Sativa L . )

Genetic variability studies provide basic information regarding the genetic properties of the population based on which breeding methods are formulated for further improvement of the crop. The estimates of heritability, coefficients of variability and genetic advance computed for 12 yield contributing traits. Genetic parameters for yield and its correspondent characters in rice were estimated from a trial with four CMS lines, fifteen testers, three checks and sixty crosses evaluated for twelve characters related to yield. In general, the magnitude of phenotypic coefficient of variation (PCV) was higher than the corresponding genotypic coefficient of variation (GCV) for all the traits, indicating that the apparent variation is not only due to genotypes but, also due to the influence of environment. Therefore, caution has to be exercised in making selection for these characters on the basis of phenotype alone as environmental variation is unpredictable in nature. High estimates of heritability and genetic advance in broad sense and narrow sense were recorded for all characters. High heritability coupled with high genetic advance in percent of mean was observed for all the traits, indicating predominance of additive gene action for these characters. Hence, simple selection based on phenotypic performance of these characters would be more effective. The estimates of additive variance ( 2 A σ ) was found higher than the dominance variance ( 2 D σ ) for all characters. The degree of dominance was greater than the unity for the characters spikelets per panicle, spikelet fertility, 1000-grain weight, biological yield per plant, L/B ratio and grain yield per plant, indicating the presence of over dominance gene action.