An Efficient Implementation of the Transportation Problem

The transportation problem is a special type of linear program in which the objective is to minimize the total cost of shipping a single commodity from a number of sources (m) to a number of destinations or sinks (n). Because of the special structure of the transportation problem, a special algorithm can be designed to find an optimal solution efficiently. Due to the large amount of information in the problem, judicious storage and management of the data are essential requirements of any viable implementation of the transportation algorithm. Using sparse matrix techniques to store the solution array, and a rooted tree as the labeling method for handling the associated information provides a viable method to solve the transportation problem. A difficult test problem was designed to test the computer program and demonstrate its efficiency. We were able to successfully implement the transportation algorithm for problems involving one million possible shipping routes. The FORTRAN code developed is included, as well as the results of several runs of the test problem

“It Takes a Village!”: Social Capital Building in a Remote Hawai‘i Community

In this cross-sectional study, we investigated the multi-level educational intervention among youth in a low-income, remote community in Hawai‘i, United States. The program aided with middle schoolers’ transition into adulthood through youth-adult partnerships, teen mentoring, and community sustainability. Drawing upon social capital framework, we explored participants’ experiences and how the intervention promoted positive developmental outcomes among the youth. We recruited youth from a rural Title I Middle School in Hawai‘i. Nine youth (nboys=6, ngirls=3; Mage=13; 44.9% Native Hawaiian or Other Pacific Islander, 44.4% Black or African American, 33.3% White, 22.2. % Asian; participants could select multiple races), teen mentors (ngirls=3; Mage=18), and an adult partner (male; 24 years old) participated in 26 virtual club meetings in Spring 2021. This qualitative study consisted of 27 participants who took part in focus groups and observations. Three themes emerged: skill development, youth-adult relationship building, and sense of belonging. These social components encouraged the sharing of knowledge and feelings among participants on horizontal and oblique directions through reciprocity and helped create a social norm of a supportive environment to make youth feel belonging to the group and the local community. Multi-level interventions that draw upon community resources and youth-adult partnerships can benefit at-risk, minority adolescent populations. We identified non-familial role models and a sense of belonging to one’s community as two key protective factors that may lead to positive cognitive changes when youth transition into adulthood

Maximizing the First-Year Planning Period for Scholarly Publications: Implications for Prospective CYFAR Grant Recipients

One of CYFAR\u27s unique features is the built-in planning year for all grant recipients. We present our evaluation team’s approach during year 1 to establish a foundation and plan for scholarly publications during funding years 2–5. The systematic literature review provided the team with a better understanding of the culture and context of the project’s target population. Collaboration between PI/Co-PI and Evaluator served as a powerful tool to achieving this goal. Not only does this model benefit future CYFAR grant recipients’ and Extension professionals’ curriculum development and program evaluation, it can also inform recruitment efforts and community partnership development

Lithium treatment reduces the renal kallikrein excretion rate

Lithium treatment reduces the renal kallikrein excretion rate. Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 39.6 mU/24 hrs (P < 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 58.4 mU/24 hrs (P < 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells

Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating&nbsp;levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health

The influence of lifestyle interventions and overweight on infertility: a systematic review, meta-analysis, and meta-regression of randomized controlled trials

This study aimed to investigate the effect of lifestyle intervention (LSI) on diagnosed infertility in overweight and obese women. A systematic review and meta-analysis were conducted. A literature search was performed on the following databases from September 2022 to December 2022: PubMed, Web of Science, and SPORTDiscus. The inclusion criteria were the following: women between 18 and 45 years of age, BMI over 25.0 kg/m2, diagnosed with infertility, a weight loss intervention, and control group part of RCTs. In total, 15 studies were identified and included. The meta-analysis shows a beneficial effect of LSI on reducing weight, waist circumference, and BMI and increasing infertility. A significantly beneficial effect of lifestyle intervention on weight reduction was observed for participants who initially had a higher BMI, while a non-significant effect was observed for individuals with a BMI above 35 kg/m2. The meta-analysis showed a beneficial effect of lifestyle intervention on ovulation incidence and sex hormone-binding globulin. The lifestyle intervention group had 11.23 times more ovulatory incidence than the control group, which in turn increased the ability to conceive. As robust evidence for the effect of lifestyle interventions on infertility in obese and overweight women was found, it is advised to integrate similar interventions into future infertility treatment processes

Substrate conformational dynamics facilitate structure-specific recognition of gapped DNA by DNA polymerase

DNA-binding proteins utilise different recognition mechanisms to locate their DNA targets; some proteins recognise specific DNA sequences, while others interact with specific DNA structures. While sequence-specific DNA binding has been studied extensively, structure-specific recognition mechanisms remain unclear. Here, we study structure-specific DNA recognition by examining the structure and dynamics of DNA polymerase I Klenow Fragment (Pol) substrates both alone and in DNA–Pol complexes. Using a docking approach based on a network of 73 distances collected using single-molecule FRET, we determined a novel solution structure of the single-nucleotide-gapped DNA–Pol binary complex. The structure resembled existing crystal structures with regards to the downstream primer-template DNA substrate, and revealed a previously unobserved sharp bend (∼120°) in the DNA substrate; this pronounced bend was present in living cells. MD simulations and single-molecule assays also revealed that 4–5 nt of downstream gap-proximal DNA are unwound in the binary complex. Further, experiments and coarse-grained modelling showed the substrate alone frequently adopts bent conformations with 1–2 nt fraying around the gap, suggesting a mechanism wherein Pol recognises a pre-bent, partially-melted conformation of gapped DNA. We propose a general mechanism for substrate recognition by structure-specific enzymes driven by protein sensing of the conformational dynamics of their DNA substrates

Fluorescent RNA cytosine analogue - an internal probe for detailed structure and dynamics investigations

The bright fluorescent cytosine analogue tCO stands out among fluorescent bases due to its virtually unquenched fluorescence emission in duplex DNA. However, like most reported base analogues, it has not been thoroughly characterized in RNA. We here report on the first synthesis and RNA-incorporation of tCO, and characterize its base-mimicking and fluorescence properties in RNA. As in DNA, we find a high quantum yield inside RNA duplexes (&lt;?F&gt; = 0.22) that is virtually unaffected by the neighbouring bases (?F = 0.20-0.25), resulting in an average brightness of 1900 M-1 cm-1. The average fluorescence lifetime in RNA duplexes is 4.3 ns and generally two lifetimes are required to fit the exponential decays. Fluorescence properties in ssRNA are defined by a small increase in average quantum yield (&lt;?F &gt; = 0.24) compared to dsRNA, with a broader distribution (?F = 0.17-0.34) and slightly shorter average lifetimes. Using circular dichroism, we find that the tCO-modified RNA duplexes form regular A-form helices and in UV-melting experiments the stability of the duplexes is only slightly higher than that of the corresponding natural RNA (&lt;?T m&gt; = + 2.3 °C). These properties make tCO a highly interesting fluorescent RNA base analogue for detailed FRET-based structural measurements, as a bright internal label in microscopy, and for fluorescence anisotropy measurements of RNA dynamics