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1.
Nature ; 590(7847): 566-570, 2021 02.
Article in English | MEDLINE | ID: mdl-33627809

ABSTRACT

When a heavy atomic nucleus splits (fission), the resulting fragments are observed to emerge spinning1; this phenomenon has been a mystery in nuclear physics for over 40 years2,3. The internal generation of typically six or seven units of angular momentum in each fragment is particularly puzzling for systems that start with zero, or almost zero, spin. There are currently no experimental observations that enable decisive discrimination between the many competing theories for the mechanism that generates the angular momentum4-12. Nevertheless, the consensus is that excitation of collective vibrational modes generates the intrinsic spin before the nucleus splits (pre-scission). Here we show that there is no significant correlation between the spins of the fragment partners, which leads us to conclude that angular momentum in fission is actually generated after the nucleus splits (post-scission). We present comprehensive data showing that the average spin is strongly mass-dependent, varying in saw-tooth distributions. We observe no notable dependence of fragment spin on the mass or charge of the partner nucleus, confirming the uncorrelated post-scission nature of the spin mechanism. To explain these observations, we propose that the collective motion of nucleons in the ruptured neck of the fissioning system generates two independent torques, analogous to the snapping of an elastic band. A parameterization based on occupation of angular momentum states according to statistical theory describes the full range of experimental data well. This insight into the role of spin in nuclear fission is not only important for the fundamental understanding and theoretical description of fission, but also has consequences for the γ-ray heating problem in nuclear reactors13,14, for the study of the structure of neutron-rich isotopes15,16, and for the synthesis and stability of super-heavy elements17,18.

2.
Cryst Growth Des ; 21(1): 396-413, 2021 Jan 06.
Article in English | MEDLINE | ID: mdl-36466627

ABSTRACT

In this work, benzene-1,3,5-tricarboxylic (trimesic acid, TMSA) and benzene-1,2,3-tricarboxylic acid (hemimellitic acid, HMLA) were used as coformers for cocrystal synthesis with chosen purine alkaloids. Theobromine (TBR) forms cocrystals TBR·TMSA and TBR·HMLA with these acids. Theophylline (TPH) forms cocrystals TPH·TMSA and TPH·HMLA, the cocrystal hydrate TPH·TMSA·2H2O and the salt hydrate (TPH)+·(HMLA)-·2H2O. Caffeine (CAF) forms the cocrystal CAF·TMSA and the cocrystal hydrate CAF·HMLA·H2O. The purine alkaloid derivatives were obtained by solution crystallization and by neat or liquid-assisted grinding. The powder X-ray diffraction method was used to confirm the synthesis of the novel substances. All of these solids were structurally characterized, and all synthons formed by purine alkaloids and carboxylic acids were recognized using a single-crystal X-ray diffraction method. The Cambridge Structural Database was used to determine the frequency of occurrence of analyzed supramolecular synthons, which is essential at the crystal structure design stage. Determining the influence of structural causes on the various synthon formations and molecular arrangements in the crystal lattice was possible using structurally similar purine alkaloids and two isomers of benzenetricarboxylic acid. Additionally, UV-vis measurements were made to determine the effect of cocrystallization on purine alkaloid solubility.

3.
J Immunol Res ; 2020: 6545921, 2020.
Article in English | MEDLINE | ID: mdl-32775467

ABSTRACT

Chronic lymphocytic leukemia (CLL) is characterized by the peripheral accumulation of neoplastic B cells and is frequently complicated by the systemic immunosuppression associated with an impairment in B and T lymphocyte activation. We hypothesized that the expression of immune checkpoint suppressors B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen (CTLA-4) is disturbed in both lymphocyte subpopulations in CLL. The expression of CTLA-4 and BTLA mRNA was determined by real-time PCR, while CTLA-4 protein expression (surface or intracellular) was estimated in BTLA+ lymphocytes by flow cytometry. In CLL patients, we observed a higher gene transcript level of BTLA and CTLA-4 than in healthy individuals in both freshly isolated and PMA stimulated B and T cells. Remarkably, lower amounts of both inhibitory proteins were found in peripheral blood (PB) CLL B cells, whereas normal BTLA and elevated CTLA-4 were found in T cells. Consistently, there was a prevalence of CTLA-4+ cells within circulating BTLA+ T cells cells of patients confronting PB healthy cells. After in vitro stimulation, the only change found in CLL patients was a decrease in BTLA expression in B and T lymphocytes. In contrast, healthy lymphocytes responded more vigorously as regards the BTLA and CTLA expression with substantially higher frequency of CD69+ cells under the stimulating condition compared to corresponding cells from the CLL group. Our results indicate that CLL development is associated with the affected expression of BTLA and CTLA-4 checkpoint receptors in PB and its impaired expression might be associated with lowering of the threshold for B cell activation and proliferation, while upregulated CTLA-4 expression in CLL peripheral BTLA+ T cells may contribute to suppressed T cell effector functions. This hypothesis needs to be validated in future studies, which would allow us to explain how the increased or decreased expression of these molecules affects the cell function.


Subject(s)
CTLA-4 Antigen/metabolism , Immune Checkpoint Proteins/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Receptors, Immunologic/metabolism , Adult , Aged , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , B-Lymphocytes/metabolism , Cell Proliferation/physiology , Cells, Cultured , Female , Humans , Lectins, C-Type/metabolism , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation/physiology , Male , Middle Aged , RNA, Messenger/metabolism , T-Lymphocytes/immunology , Up-Regulation/physiology
5.
Pathol Oncol Res ; 23(4): 837-843, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28101800

ABSTRACT

The impairment of immunological surveillance caused by aberrant T cell activation can lead to an inadequate anti-tumor response. Therefore, deregulation in co-stimulatory pathway might be associated with cancer susceptibility. Here we undertook a prospective study to investigate whether genetic variations in gene encoding molecule CD28 and CTLA-4 playing pivotal role in regulating adoptive immune response can influence susceptibility to prostate cancer. Single nucleotide polymorphisms (SNPs) in CTLA-4 and CD28 genes were genotyped in 301 prostate cancer (PCa) patients and 301 controls. The distributions of the genotypes and haplotypes in the CTLA-4/CD28 SNPs were similar in both studied groups. However, the overrepresentation of carriers of CTLA-4c.49A>G[A] allele and carriers of CTLA-4g.319C>T[T] allele in PCa as compared to controls was observed (p = 0.082 and p = 0.13, respectively). The risk of disease was higher (OR 1.78) for carriers of both susceptibility alleles as compared to carriers of protective genotypes (p = 0.03). The CTLA-4c.49A>G and CTLA-4g.319C>T SNPs might be considered as low risk susceptibility locus for PCa.


Subject(s)
CD28 Antigens/genetics , CTLA-4 Antigen/genetics , Genetic Predisposition to Disease/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/immunology , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors
6.
Tissue Antigens ; 85(6): 466-75, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25855135

ABSTRACT

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule absent from most normal tissues but detected in many malignant tumors. It is recognized by cells of the immune system using LILRB1, KIR2DL4 and LILRB2 receptors. We attempted to find out whether some polymorphisms of HLA-G, LILRB1 and KIR2DL4 genes are associated with susceptibility to nonsmall cell lung cancer (NSCLC). Four polymorphisms in HLA-G, i.e. -964A>G (rs1632947), -725C>G>T (rs1233334), -716T>G (rs2249863) in the promoter, and a 14 base pair insertion/deletion (14 bp indel) in the 3'-untranslated region (3'UTR), and five in LILRB1 - 5651G>A (rs41308748) in intron 14, 5717C>T L622L (rs1061684), 5724G>A E625K (rs16985478), 5774 C>A P641P (rs41548213) in exon 15, and 5806C>T (rs8101240) in 3'UTR - as well as 9620 9A/10A (rs11410751) polymorphism in exon 7 of KIR2DL4 were typed using different laboratory techniques. Only one single nucleotide polymorphism (SNP) in HLA-G (-964A>G) and one in LILRB1 (5724G>A) were found to influence the risk of NSCLC. In addition, 5724G>A was associated with protection from tumor cell infiltration of regional lymph nodes. Most importantly, we detected HLA-G and LILRB1 expression in tumor specimens, but no correlation with genetic polymorphisms was observed. HLA-G and LILRB1 protein expression levels in tumor tissue were significantly correlated with tumor stage.


Subject(s)
Antigens, CD/genetics , Antigens, Neoplasm/genetics , Carcinoma, Non-Small-Cell Lung/genetics , HLA-G Antigens/genetics , INDEL Mutation , Lung Neoplasms/genetics , Neoplasm Proteins/genetics , Polymorphism, Single Nucleotide , Receptors, Immunologic/genetics , Receptors, KIR2DL4/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Amino Acid Substitution , Antigens, CD/biosynthesis , Antigens, CD/immunology , Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/immunology , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Gene Expression Profiling , Gene Frequency , HLA-G Antigens/biosynthesis , HLA-G Antigens/immunology , Humans , Leukocyte Immunoglobulin-like Receptor B1 , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/immunology , Neoplasm Staging , Promoter Regions, Genetic/genetics , Receptors, Immunologic/biosynthesis , Receptors, Immunologic/immunology , Receptors, KIR2DL4/biosynthesis , Receptors, KIR2DL4/immunology , Risk , Young Adult
7.
Adv Med Sci ; 57(2): 296-301, 2012.
Article in English | MEDLINE | ID: mdl-22968341

ABSTRACT

PURPOSE: We investigated HbA1c's validity as a screening parameter for excluding dysglycemic states in the studied population. MATERIAL/METHODS: Sensitivity and specificity of HbA1c in some cut-off points were compared with diagnoses based on the oral glucose tolerance test (OGTT) in individuals diagnosed between 2009-2010. Receiver operating characteristic (ROC) analysis for HbA1c was conducted. HbA1c and OGGT measures were done in 441 people (253 women, 187 men, average age 40.1 years (18-79 years)). Based on the OGGT test 37 individuals were diagnosed as diabetic, 28 as impaired glucose tolerant (IGT) and 63 as having impaired fasting glycemia (IFG). RESULTS: A cut-off value of 6.5% HbA1c classifies diabetic subjects with a sensitivity of 45.9% and specificity of 97.5%. In the investigated population the best cut-off point (the highest sum of the sensitivity and specificity) was 5.9% HbA1c (sensitivity 86.6%, specificity 73%). HbA1c values excluding the risk of dysglycemic states have shown false negative rate in 31.9% when HbA1c was 5.5% and 10.6% when HbA1c was 5.0%. CONCLUSIONS: Our results indicate that in the investigated population the evaluation of the prevalence of type 2 diabetes using HbA1c values proposed by the American Diabetes Association (ADA) has unsatisfactory sensitivity and detects less than a half of cases of diabetes based on the OGTT diagnoses. HbA1c 5.7% does not have sufficient specificity to identify individuals not being at risk of any disorder of glucose metabolism.


Subject(s)
Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Glycated Hemoglobin/metabolism , Adolescent , Adult , Aged , False Negative Reactions , Female , Glucose Tolerance Test , Humans , Male , Mass Screening , Middle Aged , Prediabetic State/blood , Prediabetic State/diagnosis , Reproducibility of Results , Young Adult
8.
Cell Mol Biol Lett ; 6(4): 859-70, 2001.
Article in English | MEDLINE | ID: mdl-11753433

ABSTRACT

Callus was obtained from leaf explants of Cupea wrightii and Cuphea wrightii x Cuphea tolucana hybrid plants, and the plants were later regenerated. C. tolucana explants were capable of forming callus, but not of regenerating. In order to obtain callus from C. wrightii and the hybrid plants, the addition of BAP to the medium was necessary, whereas in the case of C. tolucana auxin was needed. The regeneration of the plants did not require auxin, and both forms (C. wrightii and the hybrids) regenerated in the same medium. The regeneration yield came to around 12 plants from the callus of one harvest. Some of the callus from the hybrids was subjected to colchicine treatment, which increased the number of fully fertile regenerants from 1% to almost 20%.


Subject(s)
Lythraceae/physiology , Culture Media , Hybridization, Genetic , Lythraceae/drug effects , Plant Growth Regulators/pharmacology , Plant Leaves/drug effects , Plant Leaves/physiology , Regeneration/drug effects , Regeneration/physiology , Species Specificity
9.
Cell Mol Biol Lett ; 6(3): 587-91, 2001.
Article in English | MEDLINE | ID: mdl-11598636

ABSTRACT

In order to regenerate Cuphea tolucana from hypocotyl, cotyledon and root explants, a solid culture and 8 hormone combinations were used. Only the root explants did not react to any of the media. On most of the media, the other explants formed shoots, roots or callus, or their reaction was more complex. The regeneration probably occurred via direct organogenesis. The regenerants displayed a wide variety of morphological characteristics. However, their offspring did not show any differences from plants, which had not undergone culture.


Subject(s)
Cell Culture Techniques/methods , Magnoliopsida/growth & development , Regeneration , Cotyledon/drug effects , Cotyledon/growth & development , Culture Media , Embryonic and Fetal Development/drug effects , Hypocotyl/drug effects , Hypocotyl/growth & development , Magnoliopsida/drug effects , Plant Growth Regulators/pharmacology , Plant Roots/drug effects , Plant Roots/growth & development , Plant Shoots/drug effects , Plant Shoots/growth & development , Regeneration/drug effects
10.
Med Wieku Rozwoj ; 4(2 Suppl 3): 73-88, 2000.
Article in Polish | MEDLINE | ID: mdl-11328972

ABSTRACT

OBJECTIVES: Periventricular haemorrhagic infarction observed in premature infants is associated with intraventricular haemorrhage (IVH), which leads to obstruction of the terminal veins of periventricular white matter. This lesion has characteristic ultrasonographic evolution. The objectives of this study were to determine the frequency of occurrence of periventricular haemorrhagic infarction in premature infants in intensive care unit and to evaluate the risk factors. METHODS: A total of 203 premature infants weighing less then 1500 g at birth underwent standardized cranial ultrasound between November 1997 and June 2000. RESULTS: A total of 156 premature infants with VLBW and ELBW had IVH of various degree and 17 (8,4%) had periventricular haemorrhagic infarction (PHI). 14 babies with PHI died. Among the survivors, 2 exhibit spastic hemiparesis and one had signs of tetraplegia at 6 months of age. CONCLUSIONS: This study indicates, that PHI occurs more often in neonates, who required a lot of volume expansion due to systemic hypotension. Antenatal glucocorticoid administration has a protective function.


Subject(s)
Cerebral Hemorrhage/epidemiology , Cerebral Infarction/epidemiology , Infant, Premature , Cerebral Hemorrhage/diagnostic imaging , Cerebral Infarction/diagnostic imaging , Female , Humans , Infant, Newborn , Male , Poland/epidemiology , Retrospective Studies , Risk Factors , Ultrasonography
11.
Med Wieku Rozwoj ; 4(2 Suppl 3): 65-71, 2000.
Article in Polish | MEDLINE | ID: mdl-11328971

ABSTRACT

Patent ductus arteriosus (PDA) remains a frequent problem in premature infants, particularly with very low birth weight. Left-to-right shunting through the ductus may increase the risk of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia and death. Indomethacin is the conventional pharmacologic treatment of patent ductus arteriosus (PDA). Although indomethacin is effective in closing PDA, its use may be associated with negative influences on renal, gastrointestinal and cerebral blood flow. More recently Ibuprofen has been tested; it can close the ductus arteriosus, but compared it with indomethacin, it has no negative influence on intestinal haemodynamics. On the basis of relevant literature, ibuprofen and indomethacin have been compared with regard to efficacy for closure of patent ductus arteriosus and side effects.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Ductus Arteriosus, Patent/drug therapy , Ibuprofen/therapeutic use , Indomethacin/therapeutic use , Infant, Premature , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Bronchopulmonary Dysplasia/etiology , Clinical Trials as Topic , Enterocolitis, Necrotizing/etiology , Humans , Ibuprofen/pharmacology , Indomethacin/pharmacology , Infant, Low Birth Weight , Infant, Newborn , Treatment Outcome
12.
Vopr Pitan ; (3): 38-41, 1984.
Article in Russian | MEDLINE | ID: mdl-6474949

ABSTRACT

Experiments of Wistar rats were made to compare the utilization of proteins limited by sulfur-containing amino acids or isoleucine. The score of the limiting amino acid of the proteins under study was identical (0.65). The diets included 2, 5, 10, 15, 20, 25, 30, 40 and 50 g protein per 100 g diet. Depending on the protein content in the diet, the following values of net protein utilization (NPU) were obtained for protein limited by sulfur-containing amino acids: 0.680, 0.647, 0.616, 0.600, 0.562, 0.460, 0.315, 0.240, 0.210. Meanwhile, the values for protein limited by isoleucine were 0.700, 0.697, 0.600, 0.560, 0.524, 0.450, 0.340, 0.260, 0.200. Despite insignificant differences in feed consumption and weight gains in the animals, the above cited values of the NPU did not differ essentially in terms of test protein concentration under comparison. The data obtained indicate that the biological value of proteins limited by sulfur-containing amino acids does not differ from that of proteins limited by isoleucine.


Subject(s)
Amino Acids, Sulfur/metabolism , Caseins/metabolism , Dietary Proteins/metabolism , Isoleucine/metabolism , Amino Acids, Sulfur/administration & dosage , Animal Feed , Animals , Caseins/administration & dosage , Dietary Proteins/administration & dosage , Digestion , Isoleucine/administration & dosage , Nutritive Value , Rats , Rats, Inbred Strains
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