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Biomedical subjects

C Dufour

Publications and source records attributed to C Dufour.

At least 19 recordsLinked to original sources

Skeletal unloading induces osteoblast apoptosis and targets alpha5beta1-PI3K-Bcl-2 signaling in rat bone.

The mechanisms underlying the altered osteoblastogenesis and bone loss in response to disuse are incompletely understood. Using the rat tail suspension model, we studied the effect of skeletal unloading on osteoblast and osteocyte apoptosis. Tail suspension for 2 to 7 days decreased tibial bone mass and induced early apoptotic loss of osteoblasts and delayed apoptotic loss of osteocytes. Surrenal gland weight and plasma corticosterone levels did not differ in loaded and unloaded rats at any time point, indicating that osteoblast/osteocyte apoptosis occurred independently of endogenous glucocorticoids. The mechanistic basis for the disuse-induced osteoblast/osteocyte apoptosis was examined. We found that alpha5beta1 integrin and phosphorylated phosphatidyl-inositol-3 kinase (p-PI3K) protein levels were transiently decreased in unloaded metaphyseal long bone compared to loaded bones. In contrast, p-FAK and p-ERK p42/44 levels were not significantly altered. Interestingly, the reduced p-PI3K levels in unloaded long bone was associated with decreased levels of the survival protein Bcl-2 with unaltered Bax levels, causing increased Bax/Bcl-2 levels. The results indicate that skeletal unloading in rats induces a glucocorticoid-independent, immediate increase in osteoblast apoptosis associated with decreased alpha5beta1-PI3K-Bcl-2 survival pathway in rat bone, which may contribute to the altered osteoblastogenesis and osteopenia induced by unloading.

Adrenal Glands↗

High-grade glioma in children under 5 years of age: a chemotherapy only approach with the BBSFOP protocol.

The aim of this study was to evaluate a chemotherapy strategy that avoids radiotherapy in first-line treatment of young children with high-grade glioma. A total of 21 children under 5 years of age received the BBSFOP protocol, comprising seven cycles of three drug pairs (carboplatin/procarbazine, cisplatin/etoposide and vincristine/cyclophosphamide) administered over a 16 month period. Radiotherapy was performed in case of recurrence/progression. Median age at diagnosis was 23 months. Histology was classified as World Health Organisation (WHO) grade III in 13 and grade IV in 8. Of the 13 children with a residual tumour, chemotherapy induced 2 partial responses (PR), 1 minor response (MR) and 1 stable disease (SD) with no recurrent disease. Five-year progression-free survival was 35% and 5-year overall survival was 59%, with a median follow-up of 5.2 years. At the last update, 12 children were alive (10 without radiotherapy). In conclusion, this study shows that an adjuvant chemotherapy first approach is safe and allows radiotherapy to be avoided in selected children.

Antineoplastic Combined Chemotherapy Protocols↗

[Laparoscopic surgery of deep endometriosis. About 118 cases].

OBJECTIVE: To evaluate risks and benefits of laparoscopic surgery of deep endometriosis, especially with bowel involvement with the aim of improve the inform consent of patients and choice of adequate management. PATIENTS AND METHODS: Observational continuous study on 118 patients suffering from deep endometriosis (48 with bowel endometriosis) treated by laparoscopic surgery. RESULTS: 95.6% of the patients improved their symptoms (93.7% for dyspareunia). Upon the 29 infertile patients, 21 (72%) got pregnant, including 14 (66%) spontaneously. During operative time, 3 laparotomies occurred, two of them for haemorrhage. During postoperative time, 4 major complications (2 rectal fistulas and 2 ureteral necrosis) and minor complications occurred. DISCUSSION AND CONCLUSIONS: Those data confirm the efficiency of laparoscopic treatment of deep endometriosis especially for pain relief and fertility. Nevertheless, few but severe complications may occur. Therefore, it is imperative to deliver clear, loyal and appropriate information before to proceed to such a treatment.

Adult↗

[Ifosfamide induced encephalopathy: 15 observations].

INTRODUCTION: Ifosfamide is an alkylating agent used in the treatment of germ-cell tumors, sarcomas and lymphomas. One of its main side effects is the encephalopathy of which the incidence may reach 30% in the literature, in adults and children just as well. OBJECTIVES: Based on both our experience and a review of the literature, we propose some recommendations for the management of this complication. PATIENTS AND METHODS: We report 15 encephalopathy cases in non-brain tumor patients, which occurred between January 1987 and March 2002 in children from 2 to 17 years old, treated for solid tumors at the Institut Gustave Roussy. Ifosfamide was administered at a posology between 5.4 and 15 g/m(2)/course, associated with other antimitotics such as actinomycin D, etoposide or vincristine. RESULTS: Six patients experienced a grade III neurological toxicity according to the NCI classification, which developed as excess drowsiness lasting up to 36 hours. Six other patients developed grade IV neurotoxicity, including two comas resolving within 4 days and four short generalized convulsions. Three other children experienced grade II drowsiness. Brain MRIs were normal and EEG showed an aspecific encephalopathy tracing. This early central neurotoxicity appeared right from the first administration, and occurred immediately after the first injection or during the second or third day of treatment. It was most often reversible, usually 3 to 5 days after the last ifosfamide administration. Five patients were administered a treatment with Methylene Blue with a demonstrable efficacy in only one case. No death or neurological sequelae have been noted. Ifosfamide has been renewed after the neurological accident in 7 of those patients. Only 1 of those 7 patients developed grade IV neurotoxicity during the next course of treatment. In 2 of those 7 children, Methylene Blue was used in a prophylactic way. No neurological disorders have been noted during the next courses of treatment. DISCUSSION: In the literature, the following are described as risk factors for ifosfamide encephalopathy: advanced pelvic disease, previous cisplatyl treatment and renal failure. We have not found any of these predisposing factors in our series, but three of the fifteen patients had severe neurotoxicity associated with Vincristin during previous treatments. CONCLUSION: Facing a clinical diagnosis of ifosfamide encephalopathy, it is recommended to discontinue administration of ifosfamide and inject by intravenous route 50 mg Methylene Blue every 4 hours until the symptomatology recedes. The re-challenge of Ifosfamide is not contra-indicated and should be performed under prophylactic treatment with Methylene Blue by intravenous route at the dose of 50 mg every 6 hours.

Adolescent↗

The polymorphisms -318C>T in the promoter and 49A>G in exon 1 of CTLA4 and the risk of aplastic anemia in a Caucasian population.

Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.

Adolescent↗

Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.

DNA-Binding Proteins↗

Use of odd and branched-chain fatty acids in rumen contents and milk as a potential microbial marker.

The objectives of this study were: 1) to determine if a correlation exists between rumen odd and branched-chain fatty acids (OBCFA, i.e., C(15:0), iso C(15:0), anteiso C(15:0), C(17:0), iso C(17:0), anteiso C(17:0), and C(17:1)), uracil, and purine bases (PB), 2) to evaluate the potential of milk OBCFA secretion to predict duodenal flow of microbial protein in lactating cows, 3) to evaluate the accuracy of the latter prediction equations using an independent data set, and 4) to determine whether these predictions were more accurate than predictions based on dry matter intake (DMI) and dietary characteristics. In the first experiment, 4 lactating dairy cows arranged in a 4 x 4 Latin square were offered diets based on grass silages of different botanical composition and a standard concentrate. The relationship between rumen pool size of OBCFA and microbial matter was investigated. Rumen pool size of microbial matter (g), determined 4, 12, and 17 h after feeding, using uracil and PB as microbial markers, was closely related to OBCFA (g) [r(2) = 0.716, root mean square error (RMSE) = 4.45]. To correct for differences in marker concentrations among strains of rumen microbes, C(17:0) was included in the regression equations, resulting in an increased predictive power (r(2) = 0.780, RMSE = 3.92). The relationship between microbial flow to the duodenum and milk OBCFA yield was evaluated in a second experiment with lactating dairy cows offered diets based on grass silage and concentrates differing in starch source. Similar to observations in the rumen, milk OBCFA yield was closely related to microbial flow to the duodenum (RMSE = 4.28), but predictive power of equations did not increase when straight-chain C(17)-fatty acids were included in the regression equations (RMSE = 4.92). Evaluation of the current prediction equations with 3 independent datasets resulted in a root mean square prediction error of 20.5 and 13.4% of the observed mean for equations based on milk secretion of total OBCFA and straight-chain C(17)-fatty acids, respectively. Comparison of the accuracy of the latter equations with 2 previously published equations based on DMI and dietary characteristics suggest the former to be more accurate. This first evaluation suggests that milk OBCFA could be used as a marker for duodenal flow of microbial matter, especially when accurate measurements of DMI are not available.

Animal Nutritional Physiological Phenomena↗

Occupational risk factors, ultraviolet radiation, and ocular melanoma: a case-control study in France.

BACKGROUND: Ultraviolet radiation has been suspected as a possible cause of ocular melanoma. Because this association is controversial, we examine the role of occupational exposure to ultraviolet radiation on the occurrence of this rare cancer. MATERIAL AND METHODS: A population-based case-control study was conducted in 10 French administrative areas (départements). Cases were 50 patients with uveal melanoma diagnosed in 1995-1996. Controls were selected at random from electoral rolls, after stratification for age, gender, and area. Among 630 selected persons, 479 (76%) were interviewed. Data on personal characteristics, occupational history, and detailed information on each job held were obtained from face-to-face interviews using a standardized questionnaire. Estimates of occupational exposure to solar and artificial ultraviolet light were made using a job exposure matrix. RESULTS: Results show elevated risks of ocular melanoma for people with light eye color, light skin color, and for subjects with several eye burns. The analysis based on the job exposure matrix showed a significantly increased risk of ocular melanoma in occupational groups exposed to artificial ultraviolet radiation, but not in outdoor occupational groups exposed to sunlight. An elevated risk of ocular melanoma was seen among welders (odds ratio = 7.3; 95% confidence interval = 2.6-20.1 for men), and a dose-response relationship with job duration was observed. The study also showed increased risk of ocular melanoma among male cooks, and among female metal workers and material handling operators. CONCLUSION: Following the present study, the existence of an excess risk of ocular melanoma in welders may now be considered as established. Exposure to ultraviolet light is a likely causal agent, but a possible role of other exposures in the welding processes should not be overlooked.

Case-Control Studies↗

Stem cell transplantation from HLA-matched related donor for Fanconi's anaemia: a retrospective review of the multicentric Italian experience on behalf of AIEOP-GITMO.

Twenty-seven consecutive Italian patients with Fanconi's anaemia (FA) underwent stem cell transplantation (SCT) from an HLA-matched related donor in 10 Italian centres of the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP), Gruppo Italiano di Trapianto di Midollo Osseo (GITMO). Twenty-two patients (81.5%) were conditioned with low-dose (median 20 mg/kg) cyclophosphamide (Cy) and thoraco-abdominal or total body irradiation (median dose 500 cGy), five patients (18.5%) with high-dose Cy (median 120 mg/kg). Graft-vs.-host disease (GVHD) prophylaxis was carried out with cyclosporin A in 26 cases; methotrexate (MTX) was added in eight cases. One patient received MTX alone. The median follow-up was 36 months. Ninety-two percent of patients (25 out of 27) engrafted, grade II and III acute GVHD occurred in 28% and 8% of patients, respectively, with chronic GVHD in 12.5%. Conditioning-related toxicity was mild: 4% of patients had grade III mucositis, 7.4% had grade II haemorrhagic cystitis, 14.8% had grade III liver toxicity and 11.1% had grade III renal toxicity. Transplant-related mortality at 12 months was 19.2%, survival at 36 months was 81.5%, with a median Karnofsky score of 100%. No late tumours occurred after a mean follow-up of the survivors of 5 years. None of the studied variables significantly affected the survival, including conditioning regimen, acute GVHD and clinical non-haematological phenotype. Among the studied variables, only conditioning regimens containing high-dose Cy and the presence of genital abnormalities were significantly (P < 0.05) associated with an increased rate of acute GVHD. Our study demonstrates that the Italian FA patients undergoing SCT from an HLA-matched related donor have a very good outcome. These patients, when compared with others of different ethnic origin who underwent allogeneic bone marrow transplantation, showed a less severe non-haematological phenotype, raising the possibility that this milder phenotype may have, at least in part, contributed to the outcome. Our data may provide a useful tool for further studies aiming to correlate genotype with phenotype.

Adolescent↗

Interferon gamma and tumour necrosis factor alpha are overexpressed in bone marrow T lymphocytes from paediatric patients with aplastic anaemia.

Twelve paediatric patients with aplastic anaemia and two groups of normal control subjects underwent flow cytometric analysis for intracytoplasmic expression of gamma interferon (gamma-IFN) and tumour necrosis factor alpha (TNF-alpha) in bone marrow and peripheral blood CD4+ and CD8+ cells. The same cytokines were tested, by immunoassay, in culture supernatants from unstimulated bone marrow mononuclear cells (MNCs). Marrow CD4+ and CD8+ cells expressing gamma-IFN and TNF-alpha were significantly increased in the patients in comparison with normal control subjects (P from < 0.05 to < 0.0001 in the different cellular subsets). Patients' marrow CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were significantly increased when compared with the same cell fractions from paired peripheral blood samples (P from < 0.05 to < 0.0001 in the various cellular subsets). In the supernatant of marrow MNCs, gamma-IFN and TNF-alpha were detected in four out of eight and five out of eight cases, respectively, whereas neither cytokine was traceable in the control subjects. Patients' peripheral blood CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were not significantly increased in comparison with those from normal control subjects. Whereas patients with favourable and unfavourable outcomes had no significantly different proportions of marrow gamma-IFN+/CD4+ and gamma-IFN+/CD8+ cells, the percentages of marrow CD4+ and CD8+ cells containing TNF-alpha were significantly lower in subjects with favourable than in those with unfavourable outcome. Overall, these findings show that, in aplastic patients, T cells overexpressing gamma-IFN and TNF-alpha concentrate in the bone marrow and that intracytoplasmic expression of TNF-alpha in marrow CD4+ and CD8+ cells is associated with an unfavourable clinical course.

Adolescent↗

Human-chimpanzee DNA sequence variation in the four major genes of the renin angiotensin system.

The renin angiotensin system (RAS) is involved in blood pressure control and water/sodium metabolism. The genes encoding the proteins of this system are candidate genes for essential hypertension. The RAS involves four main molecules: angiotensinogen, renin, angiotensin I-converting enzyme, and the angiotensin II type 1 receptor (encoded by the genes AGT, REN, DCP1, and AGTR1, respectively). We performed a molecular screening over 17,037 bp of the coding and 5' and 3' untranslated regions of these genes, from three to six common chimpanzees. We identified 44 single-nucleotide polymorphisms (SNPs) in chimpanzee samples, including 18 coding-region SNPs, 5 of which led to an amino acid replacement. We observed common and different features at various sites (synonymous, nonsynonymous, and noncoding) within and between the four chimpanzee genes: (1) the nucleotide diversity at noncoding sites was similar; (2) the nucleotide diversity at nonsynonymous sites was low, probably reflecting purifying selection, except for the AGT gene; (3) the nucleotide diversity at synonymous sites, which was dependent on the G+C content at the third position of the codon, was high, except for the AGTR1 gene. Comparison of the chimpanzee SNPs with those previously reported for humans identified 119 sites with fixed differences (including 62 coding sites, 17 of which resulted in amino acid differences between the species). Analysis of polymorphism within species and divergence between species shed light on the evolutionary constraints on these genes. In particular, comparison of the pattern of mutation at polymorphic and fixed sites between humans and chimpanzees suggested that the high G+C content of the DCP1 gene was maintained by positive selection at its silent sites. Finally, we propose 68 ancestral alleles for the human RAS genes and discuss the implications for their use in future hypertension-susceptibility association studies.

Angiotensinogen↗

Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO).

One hundred consecutive patients with severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), 6-methylprednisolone (6Mpred), and granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 16 years (range, 1-72 years) and median neutrophil count was 0.2 x 10(9)/L (range, 0-0.5 x 10(9)/L). Trilineage hematologic recovery (at a median interval of 96 days from treatment) was seen in 77 patients (48 complete, 29 partial) after 1 (n = 50) or more courses of ALG (n = 27). Of the 23 nonresponders, 11 patients died at a median interval of 83 days (range, 16-1132 days), 6 were considered treatment failures and underwent transplantation, and 6 were pancytopenic. Cytogenetic abnormalities were seen in 11% of patients, clonal hematologic disease in 8%, and relapse of marrow aplasia in 9%. The actuarial survival at 5 years was 87% (median follow-up 1424 days): 76% versus 98% for patients with neutrophil counts less than versus greater than 0.2 x 10(9)/L (P =.001) and 88% versus 87% for patients aged less than versus more than 16 years (P =.8). The actuarial probability of discontinuing CyA was 38%. Patients who did not achieve a white blood cell (WBC) count of 5 x 10(9)/L during G-CSF treatment have a low probability of responding (37%) and a high mortality rate (42%). This update confirms a high probability for SAA patients of becoming transfusion independent and of surviving after treatment with ALG, CyA, 6Mpred, and G-CSF, with a significant effect of neutrophil counts on outcome. Problems still remain, such as absent or incomplete responses, clonal evolution, relapse of the original disease, and cyclosporine dependence. Early transplantation, also from alternative donors, may be warranted in patients with poor WBC response to G-CSF. (Blood. 2000;95:1931-1934)

Adolescent↗

Interactions between anthocyanins and aroma substances in a model system. Effect on the flavor of grape-derived beverages.

Evaluation of the sensory quality of wine or grape-derived beverages led us to study the interactions between flavors and anthocyanins, the colored family of polyphenols. The flavylium cation-ligand complexation, resulting in copigmentation (rise in pigment visible absorption with a concomitant bathochromic shift), was investigated using visible absorption spectroscopy. Sole volatile phenols were found to markedly interact with malvidin-3,5-O-diglucoside. With series of guaiacyl-derived aroma substances, acyl-substituted ligands proved to be better copigments than alkyl-substituted ones. Association constants and 1:1 complex stoichiometry were further determined for several substrates. Decreasing binding to malvin was observed for acetosyringone, syringaldehyde, acetovanillone, vanillin, 3,5-dimethoxyphenol, and 4-ethylguaiacol. Addition of 10% ethanol lowered by one-third the association constants for malvin-ligand couples and for malvidin-3-O-glucoside with acetosyringone and syringaldehyde. The main driving force was ascribed to hydrophobicity, although this study evidenced an influence of the ligand substitution pattern on copigmentation.

Anthocyanins↗

Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients.

Bone marrow transplant (BMT) relies on the engraftment of donor hemopoietic precursors in the host marrow space. Colony forming units-fibroblasts (CFU-f), the precursor compartment for the osteogenic lineage, are essential to hemopoietic stem cell survival, proliferation and differentiation. We have studied CFU-f in donors (aged 5 months to 62 years) and in patients who had received allogeneic BMT (aged 2 months to 63 years). In donor marrows we found an inverse correlation between CFU-f frequency and age. In BMT recipients CFU-f frequencies were reduced by 60%-90% (p < 0.05) and the numbers did not recover up to 12 years after transplant. Stromal reconstitution to normal levels was found only in patients < 5 years old. In all patients studied CFU-f post-BMT were of host origin. Patients with low CFU-f levels displayed also a decreased bone mineral density (p < 0.05) and significantly reduced levels of long-term culture-initiating cells (LTC-IC) (p < 0.05). Our study demonstrates that the marrow stromal microenvironment is seriously and irreversibly damaged after BMT. Donor cells do not contribute to reconstitute the marrow microenvironment, whose residual CFU-fs remain of host origin.

Adolescent↗

Influence of wine structurally different polysaccharides on the volatility of aroma substances in a model system.

The influence of native polysaccharides on wine organoleptic quality has not been yet clarified. Hence, the effect of purified fractions of arabinogalactan-proteins (AGPs), monomeric and dimeric rhamnogalacturonans II (mRG-II and dRG-II), and mannoproteins (MPs) on the volatility of various aroma substances was examined using the exponential dilution technique. The volatility of isoamyl acetate and ethyl hexanoate in a model wine system was not affected upon addition of wine polysaccharides in the range 5-20 g/L. At higher levels, the two esters were significantly retained in solution in the presence of the protein-rich polysaccharides MP0 and AGP0 and weakly salted out in the presence of the uronic acid-rich fractions AGP4, mRG-II, and dRG-II. In addition, the volatility increase caused by dRG-II on the esters was reversed when water was used as the solvent. 1-Hexanol exhibited retention in water with four fractions in the strength order AGP0 > dRG-II > mRG-II > AGP4 but was strongly salted out in the presence of fraction MP0. Furthermore, the diacetyl activity in water was overall not modified increasing only at high concentrations of AGP4. Reference polysaccharides dextrin and dextran were used for binding strength comparison.

Gas Chromatography-Mass Spectrometry↗

Interactions between wine polyphenols and aroma substances. An insight at the molecular level.

Control of the organoleptic quality of wine or grape-derived beverages requires the study of the interactions between flavor volatiles and polyphenols. The influence of catechin and a wine highly condensed tannin fraction on the volatility of aroma substances was investigated using a dynamic headspace technique. In a hydroalcoholic solution, isoamyl acetate, ethyl hexanoate, and benzaldehyde appeared to be more retained than limonene at low catechin concentrations (0-5 g/L). The tannin fraction induced a slight decrease of benzaldehyde volatility and a salting out of limonene and had no effect on the two esters. Furthermore, investigations at the molecular level were conducted using (1)H NMR spectroscopy. Chemical shift changes registered upon addition of a ligand to a substrate kept at constant concentration allowed the determination of the dissociation constant in a 1:1 binding model. Complexation with catechin was evaluated to be similarly weak for benzaldehyde and the two esters. In addition, catechin and epicatechin displayed a higher affinity for benzaldehyde than for 3, 5-dimethoxyphenol, supporting the hypothesis of a hydrophobic driving force.

Algorithms↗