Phase Transition Thermodynamics of 1,3,5-Tris-(α-naphthyl)benzene: Theory and Experiment.

1,3,5-Tris-(α-naphthyl)benzene is an organic non-electrolyte with notable stability of an amorphous phase. Its glassy and supercooled liquid states were previously studied by spectroscopic and calorimetric methods. Despite the continuing interest in its amorphous state and, particularly, vapor-deposited glasses, the thermodynamic parameters of the vaporization of 1,3,5-tris-(α-naphthyl)benzene have not been obtained yet. Likewise, the reliable evaluation of the thermodynamic parameters of fusion below the melting point, required to establish the thermodynamic state of its glass, is still an unsolved problem. In this work, the heat capacities of crystalline and liquid phases, the temperature dependence of the saturated vapor pressures, fusion and vaporization enthalpies were determined using differential and fast scanning calorimetry and were verified using the estimates based on solution calorimetry. The structural features of 1,3,5-tris-(α-naphthyl)benzene are discussed based on the computations performed and the data on the molecular refractivity. The consistency between the values obtained by independent techniques was demonstrated.

Recognition of granulocyte-macrophage colony-stimulating factor by specific S100 proteins.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca2+-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To probe selectivity of these interactions, the affinity of recombinant human GM-CSF to dimeric Ca2+-loaded forms of 18 recombinant human S100 proteins was studied by surface plasmon resonance spectroscopy. Of them, only S100A4 protein specifically binds to GM-CSF with equilibrium dissociation constant, Kd, values of 0.3-2 µM, as confirmed by intrinsic fluorescence and chemical crosslinking data. Calcium removal prevents S100A4 binding to GM-CSF, whereas monomerization of S100A4/A6/P proteins disrupts S100A4/A6 interaction with GM-CSF and induces a slight decrease in S100P affinity for GM-CSF. Structural modelling indicates the presence in the GM-CSF molecule of a conserved S100A4/A6/P-binding site, consisting of the residues from its termini, helices I and III, some of which are involved in the interaction with GM-CSF receptors. The predicted involvement of the 'hinge' region and F89 residue of S100P in GM-CSF recognition was confirmed by mutagenesis. Examination of S100A4/A6/P ability to affect GM-CSF signaling showed that S100A4/A6 inhibit GM-CSF-induced suppression of viability of monocytic THP-1 cells. The ability of the S100 proteins to modulate GM-CSF activity is relevant to progression of various neoplasms and other diseases, according to bioinformatics analysis. The direct regulation of GM-CSF signaling by extracellular forms of the S100 proteins should be taken into account in the clinical use of GM-CSF and development of the therapeutic interventions targeting GM-CSF or its receptors.

Thermodynamic Properties of 3- and 4-Ethoxyacetanilides between 80 and 480 K.

In this work, we present a comprehensive study of the thermodynamic properties of 3-and 4-ethoxyacetanilides. The heat capacities in crystalline, liquid, and supercooled liquid states from 80 to 475 K were obtained using adiabatic, differential scanning (DSC), and fast scanning (FSC) calorimetries. The fusion enthalpies at Tm were combined from DSC measurement results and the literature data. The fusion enthalpies at 298.15 K were evaluated in two independent ways: adjusted according to Kirchhoff's law of thermochemistry, and using Hess' law. For the latter approach, the enthalpies of the solution in DMF in crystalline and supercooled liquid states were derived. The values obtained by the two methods are consistent with each other. The standard thermodynamic functions (entropy, enthalpy, and Gibbs energy) between 80 and 470 K were calculated.

Interaction of S100A6 Protein with the Four-Helical Cytokines.

S100 is a family of over 20 structurally homologous, but functionally diverse regulatory (calcium/zinc)-binding proteins of vertebrates. The involvement of S100 proteins in numerous vital (patho)physiological processes is mediated by their interaction with various (intra/extra)cellular protein partners, including cell surface receptors. Furthermore, recent studies have revealed the ability of specific S100 proteins to modulate cell signaling via direct interaction with cytokines. Previously, we revealed the binding of ca. 71% of the four-helical cytokines via the S100P protein, due to the presence in its molecule of a cytokine-binding site overlapping with the binding site for the S100P receptor. Here, we show that another S100 protein, S100A6 (that has a pairwise sequence identity with S100P of 35%), specifically binds numerous four-helical cytokines. We have studied the affinity of the recombinant forms of 35 human four-helical cytokines from all structural families of this fold to Ca2+-loaded recombinant human S100A6, using surface plasmon resonance spectroscopy. S100A6 recognizes 26 of the cytokines from all families of this fold, with equilibrium dissociation constants from 0.3 nM to 12 µM. Overall, S100A6 interacts with ca. 73% of the four-helical cytokines studied to date, with a selectivity equivalent to that for the S100P protein, with the differences limited to the binding of interleukin-2 and oncostatin M. The molecular docking study evidences the presence in the S100A6 molecule of a cytokine-binding site, analogous to that found in S100P. The findings argue the presence in some of the promiscuous members of the S100 family of a site specific to a wide range of four-helical cytokines. This unique feature of the S100 proteins potentially allows them to modulate the activity of the numerous four-helical cytokines in the disorders accompanied by an excessive release of the cytokines.

The Impact of Social Well-Being on Population Diet Nutritional Value and Antiradical Status.

The paper presents the result of assessing the antiradical status of consumers (in the context of Russia) in connection with their well-being. This approach is based on a multistage study, in which the results of sociological surveys were applied, as well as estimates of the antiradical potential (ARP) of diets obtained using neural networks, bootstrapping the chemical composition of diets, and calculating reference values using mathematical models. The paper presents data collected from residents living in the territories of at least 21 regions and cities of Russia: Magadan, Saint Petersburg, Moscow, Krasnodar, Lipetsk, Vladivostok, Novosibirsk, Omsk, Voronezh, etc. A total of 1001 people were interviewed, which, according to our calculations, gives a margin of error in value of approximately 3.1%. To calculate the lack of vitamins in the diets of residents of the Russian Federation, data on the chemical composition of food products from the FNDDS database were used. The assessment of dietary habits showed a lack of vitamins below the recommended level in 73% of Russians for vitamin D, 59% for retinol, 38% for ß-carotenes, 13% for vitamin E, and 6% for ascorbic acid. The study showed that at least 36% of the Russian population has a low antiradical status, while it was found that "poor" consumers are more likely to consume economically more expensive foods (in terms of their nutritional value). The "poor" segments of the population consume 180-305% more canned food and 38-68% more sweet carbonated drinks than other social groups, but their consumption of vegetables is 23-48% lower. On the contrary, "wealthy" consumers consume 17-25% more complex (varied) dishes, 10-68% more fresh vegetables, and 8-39% more fish. From the obtained values it follows that consumers with low levels of ARP in their diets are in a group with an increased probability of a number of "excess" diseases (diseases of the cardiovascular system, obesity, etc.). In general, the ARP values of food consumed for low-income segments of the population were 2.3 times lower (the ratio was calculated as the percentage of consumers below the level of 11,067 equivalents necessary for the disposal of free radicals generated in the human body per day) than for those who can afford expensive food (consumers with high income). A simple increase in consumption of unbalanced foods, in our opinion, will only contribute to the entry of these consumers into the "average diet trap". All this makes it imperative to develop comprehensive measures to create a new concept of public catering; otherwise, we can expect a reduction in both the health of the population and the performance of the economy of the whole country.

X-FAST: A versatile, high-throughput, and user-friendly XUV femtosecond absorption spectroscopy tabletop instrument.

We present the X-FAST (XUV Femtosecond Absorption Spectroscopy Tabletop) instrument at the University of Wisconsin-Madison. The instrument produces femtosecond extreme ultraviolet photon pulses via high-harmonic generation in the range of 40-72 eV, as well as optical pump pulses for transient-absorption experiments. The system implements a gas-cooled sample cell that enables studying the dynamics of thermally sensitive thin-film samples. This paper provides potential users with specifications of the optical, vacuum, data acquisition, and sample cooling systems of the X-FAST instrument, along with performance metrics and data of an ultrafast laser-induced phase transition in a Ni2MnGa Heusler thin film.

A simple catch: Fluctuations enable hydrodynamic trapping of microrollers by obstacles.

It is known that obstacles can hydrodynamically trap bacteria and synthetic microswimmers in orbits, where the trapping time heavily depends on the swimmer flow field and noise is needed to escape the trap. Here, we use experiments and simulations to investigate the trapping of microrollers by obstacles. Microrollers are rotating particles close to a bottom surface, which have a prescribed propulsion direction imposed by an external rotating magnetic field. The flow field that drives their motion is quite different from previously studied swimmers. We found that the trapping time can be controlled by modifying the obstacle size or the colloid-obstacle repulsive potential. We detail the mechanisms of the trapping and find two remarkable features: The microroller is confined in the wake of the obstacle, and it can only enter the trap with Brownian motion. While noise is usually needed to escape traps in dynamical systems, here, we show that it is the only means to reach the hydrodynamic attractor.

Real-world use of blinatumomab in adult patients with B-cell acute lymphoblastic leukemia in clinical practice: results from the NEUF study.

This retrospective observational study (NEUF) included adult patients with B-cell acute lymphoblastic leukemia (B-cell ALL) who had received blinatumomab for the treatment of minimal residual disease-positive (MRD+) or relapsed/refractory (R/R) B-cell ALL via an expanded access program (EAP). Patients were eligible if blinatumomab was initiated via the EAP between January 2014 and June 2017. Patients were followed from blinatumomab initiation until death, entry into a clinical trial, the end of follow-up, or the end of the study period (December 31, 2017), whichever occurred first. Of the 249 adult patients included, 109 were MRD+ (83 Philadelphia chromosome-negative [Ph-] and 26 Philadelphia chromosome-positive [Ph+]) and 140 had a diagnosis of R/R B-cell ALL (106 Ph- and 34 Ph+). In the MRD+ group, within the first cycle of blinatumomab treatment, 93% (n = 49/53) of Ph- and 64% (n = 7/11) of Ph+ patients with evaluable MRD achieved an MRD response (MRD <0.01%). Median overall survival (OS) was not reached over a median follow-up time of 18.5 months (Ph-, 18.8 [range: 5.1-34.8] months; Ph+, 16.5 [range: 1.8-31.6] months). In the R/R group, within two cycles of blinatumomab, 51% of Ph- and 41% of Ph+ patients achieved complete hematologic remission (CR/CRh/CRi), and 83% of Ph- and 67% of Ph+ MRD-evaluable patients in CR/CRh/CRi achieved an MRD response. Median (95% confidence interval) OS was 12.2 (7.3-24.2) months in the R/R Ph- subgroup and 16.3 (5.3-not estimated) months in the R/R Ph+ subgroup. This large, real-world data set of adults with B-cell ALL treated with blinatumomab confirms efficacy outcomes from published studies.

Spectromicroscopy of Nanoscale Materials in the Tender X-Ray Regime Enabled by a High Efficient Multilayer-Based Grating Monochromator.

The combination of near edge X-ray absorption spectroscopy with nanoscale X-ray imaging is a powerful analytical tool for many applications in energy technologies, catalysis, which are critical to combat climate change, as well as microelectronics and life science. Materials from these scientific areas often contain key elements, such as Si, P, S, Y, Zr, Nb, and Mo as well as lanthanides, whose X-ray absorption edges lie in the so-called tender photon energy range 1.5-5.0 keV. Neither conventional grazing incidence grating nor crystal monochromators have high transmission in this energy range, thereby yielding the tender photon energy gap. To close this gap, a monochromator setup based on a multilayer coated blazed plane grating and plane mirror is devised. The measurements show that this novel concept improves the photon flux in the tender X-ray regime by two-orders-of-magnitude enabling previously unattainable laboratory and synchrotron-based studies. This setup is applied to perform nanoscale spectromicroscopy studies. The high photon flux provides sufficient sensitivity to obtain the electronic structure of Mo in platinum-free MoNi4 nanoparticles for electrochemical energy conversion. Additionally, it is shown that the chemical bonding of nano-structures in integrated circuits can be distinguished by the electronic configuration at the Si-K edge.

Estimating the Mass of Food Components Necessary for the Utilization of Free Radical Particles in the Human Body.

The article proposes an algorithm for an approximate assessment of the molar volume of free radicals generated in the human body per day. It takes into account the act of breathing, physical activity, food consumption, the influence of unfavorable environmental conditions, exposure to xenobiotics, as well as bad habits (alcohol and tobacco smoking). A calculation of the required set of the most commonly used food products for the disposal of free radicals was made. The calculation is a structure of four blocks with the possibility of adding optional data from human population genetic studies, environmental conditions, etc. In the proposed algorithm, the results of antiradical activity (ARA) of food products are used as input, including the results of predicting antiradical activity using artificial neural networks (ANN), which we published earlier. Based on the accepted values of one equivalent (in terms of the activity of 1 µmol of ascorbic acid), it was shown (for our data) that for the utilization of all free radicals produced in the human body per day, it will take an average of ≈260 to ≈540 g of food components in terms of dry mass (including proteins, fats, carbohydrates, etc.). At the same time, for the utilization of consumed xenobiotics, from 220 mg (in terms of vitamin C) to 260 mg (in terms of acetylcysteine -NAC) of additional plastic components or 11.5-13.0 g of essential amino acids will be required, which must be taken into account when calculating diets. This approach will be useful in the development of new functional foods, as well as in assessing the possible impact of diets on human health. Another applied point of this study is related to the possibility of using these data for better detailing and selection of food products for people working in conditions of increased radiation (in space conditions), in contact with harmful substances (chemical synthesis and production), for people practicing increased physical activity (bodybuilding and sports), and for the purposes of medical nutritional therapy.

Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatics analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect the efficacy of anti-TNF treatment in various diseases.

Dendritic cells transfected with a polyepitope DNA construct stimulate an antitumor cytotoxic response in various tumors.

Dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are known to be crucial for the antitumor response and are still included in various treatment regimens in cancer immunotherapy research. In the present study, a cell-based protocol was evaluated, involving the use of original DNA constructs encoding the wide range of TAA epitopes expressed on different epithelial cancers. The constructs were transfected into in vitro-generated DCs of patients with various types of cancer, including breast, colorectal and non-small cell lung cancer. The direct cytotoxicity assay of effector cells, activated with the transfected DCs, revealed a significant increase in cytotoxicity against autologous tumor cells. The use of DNA constructs encoding a large number of TAAs for insertion into DCs in vitro, aiming to activate a T-cell response may prove to be a reliable and unified approach for immunotherapy and for the prevention of relapse in patients with epithelial cancers.

Motility of acoustically powered micro-swimmers in a liquid crystalline environment.

Suspensions of microswimmers in liquid crystals demonstrate remarkably complex dynamics and serve as a model system for studying active nematics. So far, experimental realization of microswimmers suspended in liquid crystalline media has relied on biological microorganisms that impose strict limitations on the compatible media and makes it difficult to regulate activity. Here, we demonstrate that acoustically powered bubble microswimmers can efficiently self-propel in a lyotropic liquid crystal. The velocity of the swimmers is controlled by the amplitude of the acoustic field. Histograms of swimming directions with respect to the local nematic field reveal a bimodal distribution: the swimmers tend to either fully align with or swim perpendicular to the director field of the liquid crystal, occasionally switching between these two states. The bubble-induced streaming from a swimmer locally melts the liquid crystal and produces topological defects at the tail of the swimmer. We show that the defect proliferation rate increases with the angle between the swimmer's velocity and the local orientation of the director field.

Polycapillary-boosted instrument performance in the extreme ultraviolet regime for inverse photoemission spectroscopy: erratum.

We correct values and figures for the resolution of the spectrometer, as proposed in [Opt. Express25, 31840 (2017)10.1364/OE.25.031840OPEXFF1094-4087]. The new results take into account previously unknown, incoherent phase fluctuations, caused by the polycapillary lens (PCL), and estimate the realistic performance of the instrument.

Calcium-Bound S100P Protein Is a Promiscuous Binding Partner of the Four-Helical Cytokines.

S100 proteins are multifunctional calcium-binding proteins of vertebrates that act intracellularly, extracellularly, or both, and are engaged in the progression of many socially significant diseases. Their extracellular action is typically mediated by the recognition of specific receptor proteins. Recent studies indicate the ability of some S100 proteins to affect cytokine signaling through direct interaction with cytokines. S100P was shown to be the S100 protein most actively involved in interactions with some four-helical cytokines. To assess the selectivity of the S100P protein binding to four-helical cytokines, we have probed the interaction of Ca2+-bound recombinant human S100P with a panel of 32 four-helical human cytokines covering all structural families of this fold, using surface plasmon resonance spectroscopy. A total of 22 cytokines from all families of four-helical cytokines are S100P binders with the equilibrium dissociation constants, Kd, ranging from 1 nM to 3 µM (below the Kd value for the S100P complex with the V domain of its conventional receptor, receptor for advanced glycation end products, RAGE). Molecular docking and mutagenesis studies revealed the presence in the S100P molecule of a cytokine-binding site, which overlaps with the RAGE-binding site. Since S100 binding to four-helical cytokines inhibits their signaling in some cases, the revealed ability of the S100P protein to interact with ca. 71% of the four-helical cytokines indicates that S100P may serve as a poorly selective inhibitor of their action.

Arrested-motility states in populations of shape-anisotropic active Janus particles.

The emergence of large-scale collective phenomena from simple interactions between individual units is a hallmark of active matter systems. Active colloids with alignment-dominated interparticle interactions tend to develop orientational order and form motile coherent states, such as flocks and swarms. Alternatively, a combination of self-propulsion and excluded-volume interactions results in self-trapping and active phase separation into dense clusters. Here, we reveal unconventional arrested-motility states in ensembles of active discoidal particles powered by induced-charge electrophoresis. Combining experiments and computational modeling, we demonstrate that the shape asymmetry of the particles promotes the hydrodynamically assisted formation of active particles' bound states in a certain range of excitation parameters, ultimately leading to a spontaneous collective state with arrested motility. Unlike the jammed clusters obtained through self-trapping, the arrested-motility phase remains sparse, dynamic, and reconfigurable. The demonstrated mechanism of phase separation seeded by bound state formation in ensembles of oblate active particles is generic and should be applicable to other active colloidal systems.

ExhauFS: exhaustive search-based feature selection for classification and survival regression.

Feature selection is one of the main techniques used to prevent overfitting in machine learning applications. The most straightforward approach for feature selection is an exhaustive search: one can go over all possible feature combinations and pick up the model with the highest accuracy. This method together with its optimizations were actively used in biomedical research, however, publicly available implementation is missing. We present ExhauFS-the user-friendly command-line implementation of the exhaustive search approach for classification and survival regression. Aside from tool description, we included three application examples in the manuscript to comprehensively review the implemented functionality. First, we executed ExhauFS on a toy cervical cancer dataset to illustrate basic concepts. Then, multi-cohort microarray breast cancer datasets were used to construct gene signatures for 5-year recurrence classification. The vast majority of signatures constructed by ExhauFS passed 0.65 threshold of sensitivity and specificity on all datasets, including the validation one. Moreover, a number of gene signatures demonstrated reliable performance on independent RNA-seq dataset without any coefficient re-tuning, i.e., turned out to be cross-platform. Finally, Cox survival regression models were used to fit isomiR signatures for overall survival prediction for patients with colorectal cancer. Similarly to the previous example, the major part of models passed the pre-defined concordance index threshold 0.65 on all datasets. In both real-world scenarios (breast and colorectal cancer datasets), ExhauFS was benchmarked against state-of-the-art feature selection models, including L1-regularized sparse models. In case of breast cancer, we were unable to construct reliable cross-platform classifiers using alternative feature selection approaches. In case of colorectal cancer not a single model passed the same 0.65 threshold. Source codes and documentation of ExhauFS are available on GitHub: https://github.com/s-a-nersisyan/ExhauFS.

Cr/C lamellar multilayer grating in conical diffraction mounting for beam splitter used in X-ray free-electron lasers.

A lamellar multilayer grating in a conical diffraction mounting was proposed as a beam splitter for X-ray free-electron lasers. Theoretical calculations demonstrated that the distribution of diffraction efficiency can be adjusted by optimizing the groove depth or d-spacing. A Cr/C multilayer lamellar grating with a line density of approximately 2500 L/mm was fabricated. The performance of the element was measured in the Optics Beamline PM-1 (BESSY-II) at an energy of 1500 eV. A five-order diffraction pattern was recognized, and the diffraction efficiencies of the -/+first-order were approximately 12.6 and 4.4%, respectively. The asymmetric distribution of diffraction efficiency can be caused by the different sidewall angles of the grating groove.

Isatuximab monotherapy in patients with refractory T-acute lymphoblastic leukemia or T-lymphoblastic lymphoma: Phase 2 study.

The poor prognosis of acute T-cell lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in older adults and patients with relapsed/refractory illness is an unmet clinical need, as there is no defined standard of care and there are few treatment options. Abnormally elevated CD38 expression in T-ALL and T-LBL is associated with tumor expansion and disease development, making CD38 a potential target for anti-T-ALL and T-LBL treatment. Isatuximab is a monoclonal antibody that binds to a specific epitope on CD38. The purpose of the study was to assess the efficacy and safety of isatuximab monotherapy in a phase 2, multicenter, one-arm, open-label study in patients with relapsed or refractory T-ALL or T-LBL (Clinical Trials.gov identifier NCT02999633). The primary endpoint was to assess the efficacy of isatuximab by overall response rate (ORR). An interim analysis based on the efficacy and safety of isatuximab in the first 19 patients enrolled was scheduled, however only 14 patients were enrolled in the study. No patient achieved complete response (CR) or CR with incomplete peripheral recovery. Most patients (11 [78.6%]) developed progressive disease and had progressive disease as their best response. A total of 10 (71.4%) patients had treatment emergent adverse events considered treatment-related, with infusion reactions as the most frequent drug-related TEAE, occurring in 8 (57.1%) patients. Despite the low efficacy of isatuximab in the current study, it is likely that the use of immunotherapy medication in T-ALL will be expanded through logically targeted approaches, together with advances in the design of T-cell therapy and clinical experience and will provide restorative options beyond chemotherapy and targeted treatments.

Erythropoietin Interacts with Specific S100 Proteins.

Erythropoietin (EPO) is a clinically significant four-helical cytokine, exhibiting erythropoietic, cytoprotective, immunomodulatory, and cancer-promoting activities. Despite vast knowledge on its signaling pathways and physiological effects, extracellular factors regulating EPO activity remain underexplored. Here we show by surface plasmon resonance spectroscopy, that among eighteen members of Ca2+-binding proteins of the S100 protein family studied, only S100A2, S100A6 and S100P proteins specifically recognize EPO with equilibrium dissociation constants ranging from 81 nM to 0.5 µM. The interactions occur exclusively under calcium excess. Bioinformatics analysis showed that the EPO-S100 interactions could be relevant to progression of neoplastic diseases, including cancer, and other diseases. The detailed knowledge of distinct physiological effects of the EPO-S100 interactions could favor development of more efficient clinical implications of EPO. Summing up our data with previous findings, we conclude that S100 proteins are potentially able to directly affect functional activities of specific members of all families of four-helical cytokines, and cytokines of other structural superfamilies.