Foster-Miller (United States)

Background/Objectives: Nature has evolved millions of venom-derived peptides with diverse biological functions, a substantial fraction of which target complex membrane proteins such as G-protein-coupled receptors and ion channels. Many of these peptides are stabilized by multiple disulfide bonds, endowing them with exceptional structural stability and favorable pharmacological properties. Methods: Leveraging this natural diversity, we developed a robust venom peptide therapeutics discovery system built on phage display technology and constructed a library using approximately 482 venom-derived scaffolds. The library design was guided by a machine learning (ML) model capable of predicting mutation-tolerant residues that preserve peptide foldability, maximizing structural integrity and sequence diversity. Results: The resulting VCX library was evaluated through screening against four diverse targets (CD47, DLL3, IL33, and P2X7R), yielding strong binders for all four, a success rate of 100%. Furthermore, by integrating high-throughput recombinant expression of thioredoxin-venom fusion proteins along with ML-assisted affinity maturation, we rapidly identified potential leads for DLL3 binders. Conclusions: This venom-based discovery platform offers significant advantages in both functionality and developability compared with conventional peptide discovery approaches. By combining natural structural diversity, ML-guided design, and recombinant expression, it enables efficient identification of "antibody-like" binders with molecular weights much smaller than those of antibodies. Consequently, it provides a powerful strategy for developing next-generation peptide therapeutics targeting challenging protein-protein interactions and complex membrane proteins.

Ushbu maqolada Geranium sanguineum L. turining introduksiya sharoitida o‘sishi, rivojlanishi hamda bioekologik xususiyatlari o‘rganildi. O‘simlikning morfologik belgilaridagi o‘zgarishlar, fenologik fazalari, ekologik omillarga moslashuvi tahlil qilindi. Tadqiqot natijalari introduksiya sharoitida ushbu turning yuqori moslashuvchanlikka ega ekanligini ko‘rsatdi.

This scientific article analyzes phraseological units (phrases) used in the novel "Night and Day" by Abdulkhamid Cholpon, a major figure in Uzbek literature. In the process of analysis, the stylistic features and linguistic and cultural significance of phrases in enhancing the impact of the literary text, illuminating the mental state and character of the characters, as well as revealing the idea of the work are studied

Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease that often leads to loss of speech, swallowing restrictions, respiratory failure, paralysis, and total physical dependence, despite preserved cognitive function. For some affected individuals, the anticipated decline in autonomy associated with ALS leads to the consideration of medical aid in dying (MAiD). In the United States (US), MAiD is legally permitted in 12 jurisdictions (11 states and Washington, DC); however, most require patients to self-administer the prescribed medications. This stipulation creates an inequitable barrier for people with late-stage ALS, as the ability to swallow medication or manipulate delivery devices is often lost well before the end of life. Patients with ALS who are considering MAiD and otherwise meet all eligibility criteria must weigh the decision to end their lives earlier than desired against the risk of prolonging life and becoming physically unable to self-administer MAiD. This paper, coauthored by a patient with bulbar-onset ALS, integrates clinical literature, legal analysis, and lived experience to examine how existing MAiD statutes in the US fail to accommodate the physical disabilities of otherwise eligible patients from using this option. Overall, legislative reform in the US is urgently needed to ensure that MAiD eligibility is based on informed consent and clinical criteria without unfair exclusion based on physical disability.

Free-space quantum key distribution (QKD) represents a groundbreaking advancement in secure communication, enabling secure key exchange over vast distances and offering robust encryption for the future quantum internet. However, the compatibility between fiber and free-space infrastructures continues to pose challenges for QKD protocols. Indeed, free-space and fiber-based networks commonly use different wavelengths and qubits encoding schemes. On the one hand, free-space QKD typically exploits visible light for its beneficial beam divergence compared with longer wavelengths, and polarization encoding for its robustness against turbulence. On the other hand, fiber-based QKD employs infrared light, particularly the C-band, because it shows the minimum losses with silica fibers, and time-bin encoding, due to polarization instability in optical fibers. In our study, we demonstrate the viability of a time-bin encoded QKD protocol operating in the C-band through horizontal turbulent free-space channels. We test the setup into a 50-m- and a 500-m-long link, respectively achieving an average secure key rate of 793 kbps and 40 kbps over several hours of measurements. The results encourage further exploration of the interoperability between free-space and fiber-based infrastructures, opening new possibilities for connecting terminal users with satellites in hybrid infrastructures.

Heart failure (HF) with preserved ejection fraction (HFpEF) carries a high mortality and remains a major therapeutic challenge. Effective, targeted therapies capable of reversing HFpEF pathophysiology are urgently needed. We previously demonstrated that activation of the cardiac growth hormone-releasing hormone (GHRH) pathway using high potency synthetic agonists of GHRH (GHRH-agonists: MR-356 and MR-409) improves the HFpEF phenotype in both large and small animal models, including in a murine model of cardiometabolic HFpEF (High fat diet + the nitric oxide synthase inhibitor L-NAME [HFD+L-NAME]). Here we sought to define the downstream signaling pathways responsible for this effect. A transcriptomic screen in human iPSC-derived cardiomyocytes (hiPSC-CMs) identified the hypoxia-inducible factor (HIF)-1α pathway as being activated by GHRH receptor (GHRHR) signaling, revealing an oxygen-independent mechanism of HIF-1α activation. Based on this finding, we investigated the interaction between the cardioprotective effects of the GHRH-agonist MR-356 and HIF-1α pathway activation in the murine HFD+L-NAME model of cardiometabolic HFpEF. We generated a cardiomyocyte-specific HIF-1α knockout (HIF-1α CM KO) mouse line and demonstrated that our previously reported beneficial effects of GHRH-agonist administration were completely abolished in HIF-1α CM KO mice. Together, these findings establish the GHRHR-HIF-1α axis as a central pathway integrating metabolic and contractile remodeling, suggesting that therapeutic targeting of this axis represents a novel disease-modifying approach to treating cardiometabolic HFpEF.

Yurtimizda qish faslida o‘ta sovuq ob-havo asalarilar nobud bo‘lishiga sabab bo‘ladi va atrof-muhitga tashlab yuboriladi. Apis mellifera jonsiz asalari asosida olingan xitozan (AmCS) ekologik jihatdan oqilona yechim hisoblanadi, chunki bu jarayon chiqindilarni qayta ishlashga yordam beradi. Ushbu maqolada suvda Pb(II) ionlarini inversion-voltamperometrik usulda mahalliy xomashyo hisoblangan AmCS bilan modifikatsiyalangan uglerod pastali sensor tayyorlash va elektrokimyoviy qo‘llash keltirilgan. Eksperimental parametrlar, fon elektrolitining ta’siri, pH ta’sir, elektrod yuzasiga to‘planish vaqti o‘rganildi. Eng yaxshi natija 60% (m/m) grafit kukuni, 20% (m/m) xitozan va 20% (m/m) mineral moydan iborat tarkibli elektrod, pH 6,5 da, 0,1 mol/l NaNO3 fon elektroliti, Pb(II) konsentratsiya potensiali -430 mV, vaqt 120 sekund bilan kuzatildi. Taklif qilingan sensor orqali suv namunasi tahlil qilindi betaraf usullar bilan solishtirildi.

Mamlakatimiz o‘simliklar dunyosining xilma-xilligi bilan ajralib turadi. Hozirgi vaqtda yer yuzining turli hududlaridan keltirilgan o‘simliklar introduksiya qilinishi natijasida floramiz yanada boyitilmoqda. Tabiiy va introduksiya qilingan istiqbolli o‘simliklardan unumli foydalanish maqsadida ularning bioekologiyasini, morfologiyasini, biotexnologiyasini va boshqa foydali xususiyatlarini chuqur o‘rganib, ularni xalq xo‘jaligiga tadbiq etish hozirgi kunning dolzarb masalalaridan biri hisoblanadi. Introduksiya qilingan istiqbolli o‘simliklardan biri Azolla caroliniana willd bo‘lib, xalq xo‘jaligining turli jabhalarida qo‘llash zamon taqazosi bo‘lgani uchun, bu o‘simlikning bioekologik xususiyatlarini o‘rganish zaruriyati tug‘ildi.

Mazkur maqolada, bizgacha yetib kelgan tarixiy manbaalarni o‘rganish natijasida, jamiyatda muhim o‘rin egallagan pul, xisob-kitob asosida amalga oshiriladigan iqtisodiy munosabatlar bir necha asrlar avval paydo bo‘lib, yillar davomida rivojlanib kelayotganligini ko‘ramiz. Iqtisodning tarkibiy qismi bo‘lgan moliya-budjet, g‘azna, soliq, boj sohalarida to‘g‘ri siyosatni amalga oshirish jamiyat taraqqiyotini belgilovchi muhim omillardan biri xisoblanadi. Boshqa tillarda bo‘lgani kabi o‘zbek tilida ham iqtisodiy-moliyaviy terminlarining tarkib topishi, shakllanishi va rivojlanishi o‘z tarixiy taraqqiyot yo‘lini bosib o‘tganligi va bu haqida ma’lumotlar o‘z aksini topgan.