Nowadays, the volume of databases that financial companies manage is so great that it has become necessary to address this problem, and the solution to this can be found in Big Data techniques ...applied to massive financial datasets for segmenting risk groups. In this paper, the presence of large datasets is approached through the development of some Monte Carlo experiments using known techniques and algorithms. In addition, a linear mixed model (LMM) has been implemented as a new incremental contribution to calculate the credit risk of financial companies. These computational experiments are developed with several combinations of dataset sizes and forms to cover a wide variety of cases. Results reveal that large datasets need Big Data techniques and algorithms that yield faster and unbiased estimators. Big Data can help to extract the value of data and thus better decisions can be made without the runtime component. Through these techniques, there would be less risk for financial companies when predicting which clients will be successful in their payments. Consequently, more people could have access to credit loans.
Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based ...chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.
•Platinum-based chemotherapy remains the most active treatment for ovarian cancer.•Platinum should not be withheld after response to last platinum and a treatment-free interval of <6 months.•We propose to move beyond the definition of platinum resistance to a therapy-oriented definition of platinum eligibility.•Platinum-non-eligible ovarian cancer patients are those with progression on or immediately after their last platinum.
The biogenesis and function of the mitochondrial respiratory chain (RC) involve the organization of RC enzyme complexes in supercomplexes or respirasomes through an unknown biosynthetic process. This ...leads to structural interdependences between RC complexes, which are highly relevant from biological and biomedical perspectives, because RC defects often lead to severe neuromuscular disorders. We show that in human cells, respirasome biogenesis involves a complex I assembly intermediate acting as a scaffold for the combined incorporation of complexes III and IV subunits, rather than originating from the association of preassembled individual holoenzymes. The process ends with the incorporation of complex I NADH dehydrogenase catalytic module, which leads to the respirasome activation. While complexes III and IV assemble either as free holoenzymes or by incorporation of free subunits into supercomplexes, the respirasomes constitute the structural units where complex I is assembled and activated, thus explaining the significance of the respirasomes for RC function.
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► Mitochondrial respirasome biogenesis is a multistep biosynthetic process ► It does not require the associations of independent preassembled RC complexes ► A CI intermediate acts as a scaffold for the incorporation of free CIII+CIV subunits ► Respirasomes are the structural units in which CI is fully assembled and activated
We prove that a parabolic subgroup P contained in another parabolic subgroup P’ of an Artin group A is a parabolic subgroup of P’. This answers a question of Godelle which is not obvious despite ...appearances. In order to achieve our result we construct a set-retraction A \to P of the inclusion map from a parabolic subgroup P into A. This retraction was implicitly constructed in a previous paper by Charney and the second author Bull. Lond. Math. Soc. 46 (2014), pp. 1248–1255.
Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade ...showed low objective response rates (ORR) in ROC with no identified predictive biomarker.
This phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12months and cohort B received four to six prior lines with a PFI/TFI of ≥3months. Pembrolizumab 200mg was administered intravenously every 3weeks until cancer progression, toxicity, or completion of 2years. Primary end points were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS<1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1months for both cohorts. Median OS was not reached for cohort A and was 17.6months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials.
Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response.
Clinicaltrials.gov, NCT02674061
Orbital invariant position space techniques are used to show a theoretical link between the conventional concept of bond order and the energetics of chemical interactions. Taking advantage of the ...parallelism between the covalent and ionic interaction energies in the interacting quantum atoms (IQA) approach, a real space ionic bond order is defined. Expanding the covalent and ionic interaction energies as a multipolar series we show that the zeroth order terms in the expansion, those dominating the total interaction, are nothing but distance-scaled bond orders. A chemically intuitive picture emerges in which bonding is brought about by the Coulomb attraction of permanently transferred electrons, that give rise to ionic terms, and of the Coulombic attraction of half the shared pairs, which provide the covalent contributions. A set of representative molecules are examined to explore how the zeroth order approximation works. We show that, as expected, the approximation improves with interatomic distance.
Chemical equilibrium has proven extremely useful for predicting the chemical composition of AGB atmospheres. Here we use a recently developed code and an updated thermochemical database that includes ...gaseous and condensed species involving 34 elements to compute the chemical equilibrium composition of AGB atmospheres of M-, S-, and C-type stars. We include for the first time Ti
C
clusters, with
= 1-4 and
= 1-4, and selected larger clusters ranging up to Ti
C
, for which thermochemical data are obtained from quantum-chemical calculations. Our main aims are to systematically survey the main reservoirs of each element in AGB atmospheres, review the successes and failures of chemical equilibrium by comparing it with the latest observational data, identify potentially detectable molecules that have not yet been observed, and diagnose the most likely gas-phase precursors of dust and determine which clusters might act as building blocks of dust grains. We find that in general, chemical equilibrium reproduces the observed abundances of parent molecules in circumstellar envelopes of AGB stars well. There are, however, severe discrepancies of several orders of magnitude for some parent molecules that are observed to be anomalously overabundant with respect to the predictions of chemical equilibrium. These are HCN, CS, NH
, and SO
in M-type stars, H
O and NH
in S-type stars, and the hydrides H
O, NH
, SiH
, and PH
in C-type stars. Several molecules have not yet been observed in AGB atmospheres but are predicted with non-negligible abundances and are good candidates for detection with observatories such as ALMA. The most interesting ones are SiC
, SiNH, SiCl, PS, HBO, and the metal-containing molecules MgS, CaS, CaOH, CaCl, CaF, ScO, ZrO, VO, FeS, CoH, and NiS. In agreement with previous studies, the first condensates predicted to appear in C-rich atmospheres are found to be carbon, TiC, and SiC, while Al
O
is the first major condensate expected in O-rich outflows. According to our chemical equilibrium calculations, the gas-phase precursors of carbon dust are probably acetylene, atomic carbon, and/or C
, while for silicon carbide dust, the most likely precursors are the molecules SiC
and Si
C. In the case of titanium carbide dust, atomic Ti is the major reservoir of this element in the inner regions of AGB atmospheres, and therefore it is probably the main supplier of titanium during the formation of TiC dust. However, chemical equilibrium predicts that large titanium-carbon clusters such as Ti
C
and Ti
C
become the major reservoirs of titanium at the expense of atomic Ti in the region where condensation of TiC is expected to occur. This suggests that the assembly of large Ti
C
clusters might be related to the formation of the first condensation nuclei of TiC. In the case of Al
O
dust, chemical equilibrium indicates that atomic Al and the carriers of Al-O bonds AlOH, AlO, and Al
O are the most likely gas-phase precursors.
Colon cancer has a high prevalence worldwide and is a serious public health problem. Early diagnosis greatly improves its prognosis and, among the existing methods, the detection of fecal occult ...blood is the only noninvasive test recommended for screening of the disease. To promote its massive application as a screening tool for asymptomatic populations in low-resource settings, the availability of a reliable and cost-effective method is imperative. Here, we describe the development and validation of a sensitive nanobody-based immunoassay for the detection of hemoglobin in human fecal samples. The nanobodies were selected from a library generated from a llama immunized with human hemoglobin, using a high-throughput platform that enabled the identification of the best nanobody pair. The assay allowed a sub-ng/mL limit of detection to be reached in phosphate-buffered saline, and was validated with stool samples, showing excellent reproducibility (CV% < 15 inter-day precision) and accuracy at 2 and 4 μg of hemoglobin per gram of feces, which are well below the recommended cutoff for this test (10–20 μg/g). Moreover, no cross-reactivity was observed with a panel of dietary non-human hemoglobins removing the need for pre-test dietary restrictions. Considering that the monodomain nature of nanobodies facilitates their straightforward and low-cost production by bacterial fermentation, with their provided sequences and using synthetic genes, the assay reported here could be replicated in any laboratory to perform thousands of tests for early detection of colorectal cancer at almost no cost.
Graphical abstract
Abstract
We report new results from quantum calculations of energy-transfer processes taking place in interstellar environments and involving two newly observed molecular species: C
5
N
−
and C
7
N
−
...in collision with He atoms and p–H
2
molecules. These species are part of the anionic molecular chains labeled as cyanopolyynes, which have been observed over the years in molecule-rich circumstellar envelopes and in molecular clouds. In the present work, we first carry out new ab initio calculations for the C
7
N
−
interaction potential with He atoms and then obtain state-to-state rotationally inelastic cross sections and rate coefficients involving the same transitions, which have been observed experimentally by emission in the interstellar medium (ISM) from both of these linear species. For the C
5
N
−
/He system, we extend the calculations already published in Biwas et al. to compare more directly the two molecular anions. We extend further the quantum calculations by also computing in this work collision rate coefficients for the hydrogen molecule interacting with C
5
N
−
, using our previously computed interaction potential. Additionally, we obtain the same rate coefficients for the C
7
N
−
/H
2
system by using a scaling procedure that makes use of the new C
7
N
−
/He rate coefficients, as discussed in detail in the present paper. Their significance in affecting internal state populations in ISM environments where the anionic cyanopolyynes have been found is analyzed by using the concept of critical density indicators. Finally, similarities and differences between such species and the comparative efficiency of their collision rate coefficients are discussed. These new calculations suggest that, at least for the case of these longer chains, the rotational populations could reach local thermal equilibrium conditions within their observational environments.
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